Showing papers in "Journal of B.U.ON. : official journal of the Balkan Union of Oncology in 2016"

Cervical cancer: screening, diagnosis and staging.

Abstract: Purpose: Despite the widespread screening programs, cervical cancer remains the third most common cancer in developing countries. Based on the implementation of cervical screening programs with the referred adoption of improved screening methods in cervical cytology with the knowledge of the important role of the human papilloma virus (HPV) it's incidence is decreased in the developed world. Even if cervical HPV infection is incredibly common, cervical cancer is relatively rare. Depending on the rarity of invasive disease and the improvement of detection of pre-cancerous lesions due to the participation in screening programs, the goal of screening is to detect the cervical lesions early in order to be treated before cancer is developed. In populations with many preventive screening programs, a decrease in cervical cancer mortality of 50-75% is mentioned over the past 50 years. The preventive examination of vagina and cervix smear, Pap test, and the HPV DNA test are remarkable diagnostic tools according to the American Cancer Association guidelines, in the investigation of asymptomatic women and in the follow up of women after the treatment of pre-invasive cervical cancer. The treatment of cervical cancer is based on the FIGO 2009 cervical cancer staging.

Vasculogenic mimicry and tumor metastasis.

Abstract: Vasculogenic mimicry (VM), a microvascular channel made up of nonendothelial cells, has been accepted as a new model of neovascularization in aggressive tumors, owning to the specific capacity of malignant cells to form vessel-like networks which provide sufficient blood supply for tumor growth. Multiple molecular mechanisms, especially vascular endothelial (VE)-cadherin, erythropoietin-producing hepatocellular receptor A2 (EphA2), phosphatidyl inositol 3-kinase (PI3K), matrix metalloproteinases (MMPs), vascular endothelial growth factor receptor (VEGFR1), and hypoxia inducible factor (HIF)-1a, have been reported to participate in VM formation which is associated with tumor migration and invasion. In addition, hypoxia, cancer stem cells (CSCs) and epithelial-mesenehymal transition (EMT) are regarded as significant factors in VM formation and tumor metastasis. Due to the important effects of VM on tumor progression, a review was carried out in the present study, to synthetically analyze the relationship between VM and tumor metastasis.

Curcumin (Turmeric) and cancer.

Abstract: Curcumin is a substance obtained from the root of the turmeric plant, which has the feature of being a yellow or orange pigment. It is also the main component of curry powder commonly used in Asian cuisine. Curcumin, a substance that has had an important place in traditional Indian and Chinese medicines for thousands of years, has been the center of interest for scientific studies especially in the field of cancer treatment for several years. Laboratory studies have presented some favorable results in terms of curcumin's antioxidant, antiinflammatory and anticancer properties in particular. However, since such findings have yet to be confirmed in clinical studies, its effect on humans is not clearly known. Therefore, when its advantages in terms of toxicity, cost and availability as well as the favorable results achieved in laboratory studies are considered, it would not be wrong to say that curcumin is a substance worth being studied. However, for now the most correct approach is to abstain from its use for medical purposes due to lack of adequate reliable evidence obtained from clinical studies, and because of its potential to interfere with other drugs.

Incidence, mortality, and epidemiological aspects of cancers in Iran; differences with the world data

Abstract: Purpose: No comprehensive study of cancer incidence and mortality exists in Iran. This study aimed to evaluate the incidence, mortality and epidemiological aspects of cancers in our country. Methods: In this study, information of cancer incidence and mortality in Iran was retrieved from International Cancer Registry data and reported by numbers, crude and standardized incidence and mortality rates. Cancer incidence and mortality in Iran were mapped and compared with neighboring countries and the world. Results: A total of 84,829 cancer cases occurred in Iran in 2012. Overall, 39,991 cases (47.14) were women and 44,838 (52.85) men with male to female ratio 1.12. There were 53,350 deaths, of which 43.55 in women and 56.44 in men. The sex ratio of mortality was 1.29. Five cancers with the highest standardized incidence rates (SIR) were breast cancer (28.1), gastric cancer (15.2), prostate cancer (12.6), colorectal cancer (11.1), and esophageal cancer (8.6). Five cancers with the highest standardized mortality rates (SMR) were gastric cancer (12.9), breast cancer (9.9), esophageal cancer (7.8), lung cancer (6.9) and colorectal cancer (6.6). Conclusion: Our findings revealed that the incidence of some cancers increased compared to reports in previous years. The incidence and mortality were higher in men than in women. Common cancers should be detected early using screening tests such as colonoscopy and mammography. The tests can be especially useful in old age. Additional studies should be performed to investigate the causes of cancer incidence and mortality.

Elevated expression of matrix metalloproteinase-3 in human osteosarcoma and its association with tumor metastasis

Abstract: Purpose Matrix metalloproteinase-3 (MMP-3) is one of the several MMPs that is associated with malignant tumors of breast, colon, cervix and lung, where its expression has been correlated with tumor invasion and metastasis. However, the role of MMP-3 in metastasis of osteosarcoma has not yet been explored. Methods MMP-3 expression in 15 primary and metastatic osteosarcomas with case-matched adjacent non-tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. Further, MMP-3 mRNA and protein levels were also determined in osteoblast and osteosarcoma cell lines. Additionally, migration and invasion assays were performed in MMP-3 knockdown cells. Results MMP-3 was expressed in 86.6% (13/15) of the osteosarcoma patients and its expression was significantly higher in metastatic tumors as compared to the primary osteosarcoma tumor tissues. Furthermore, osteosarcoma cell lines showed higher MMP-3 expression as compared to osteoblast cell lines. siRNA mediated MMP-3 knockdown in osteosarcoma cell lines significantly inhibited their migration and invasion properties. Conclusion Our results demonstrated that MMP-3 expression is deregulated in osteosarcomas and this potentially contributes to metastasis and might be a promising marker for the prognosis and therapy of metastatic osteosarcoma.

Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway.

Abstract: Purpose In the current study the antiproliferative effect of arctigenin, plant lignin, was evaluated on human colon cancer cell line HT-29. Furthermore, attempts were made to explore the signaling mechanism which may be responsible for its effect. Methods Cell growth inhibition was assessed by MTT and LDH assays. Flow cytometric analysis was performed to determine cell arrest in the cell cycle phase and apoptosis. Furthermore, to confirm the apoptotic activity of arctigenin, caspase-9 and -3 activities analysis was performed. The levels of reactive oxygen species (ROS) and p38 mitogen activated protein kinase (MAPK) were investigated to determine their role in inducing apoptosis in arctigenin-treated HT-29 colon cancer cell line. Results MTT and LDH results demonstrated significant cell growth inhibitory effect of arctigenin on HT-29 cells in a dose-dependent manner. Furthermore, increase in cell number arrested at G2/M phase was observed in flow cytometric analysis upon arctigenin treatment. In addition, arctigenin increased the apoptotic ratio in a dose-dependent manner. The involvement of intrinsic apoptotic pathway was indicated by the activation of caspase-9 and -3. Moreover, increased ROS production, activation of p38 MAPK and changes in mitochondrial membrane potential (ΔΨm) also revealed the role of intrinsic apoptotic signaling pathway in cell growth inhibition after arctigenin exposure. Conclusion Arctigenin induces apoptosis in HT-29 colon cancer cells by regulating ROS and p38 MAPK pathways.

Ginseng and cancer.

Abstract: Derived from the Greek word Panacea that means 'cure for all', Ginseng (Panax) has had an important place in Chinese Medicine for many of years. As the name suggests, it is believed to be a miraculous plant effective in the treatment of many health problems. It is claimed to have many effects such as sedative, hypnotic, aphrodisiac, antidepressant, diuretic, and stimulating effects, and to be effective in the treatment of certain health problems such as diabetes, Alzheimer's disease, erectile dysfunction and infections. In addition, its effects on the prevention and treatment of cancer as well as on the reduction of cancer-related symptoms have been prioritized in recent years. However, the studies that have been done so far do not confirm these effects. Although certain favorable results have been obtained in some studies intended for investigating its effects on acute nasopharyngitis, diabetes, Alzheimer's disease, and erectile dysfunction, it is early to say anything conclusive. And in cancer patients, it has been shown to be effective in reducing weakness due to cancer and its treatment. On the other hand, ginseng may cause important drug interactions, although it is described as a relatively safe product. For now, it seems to be reasonable to use ginseng only for cancer-related weakness in cancer patients at this point. But this should definitely be done within the knowledge and under the control of oncologists.

Ganoderma Lucidum (Reishi Mushroom) and cancer.

Abstract: Having a long historical past in traditional Chinese medicine, Ganoderma Lucidum (G. Lucidum) is a type of mushroom believed to extend life and promote health. Due to the increasing consumption pattern, it has been cultivated and marketed intensively since the 1970s. It is claimed to be effective in the prevention and treatment of many diseases, and in addition, it exerts anticancer properties. Almost all the data on the benefits of G. Lucidum are based on laboratory and preclinical studies. The few clinical studies conducted are questionable. Nevertheless, when the findings obtained from laboratory studies are considered, it turns that G. Lucidum is likely to have some benefits for cancer patients. What is important at this point is to determine the components that will provide these benefits, and use them in drug development, after testing their reliability. In conclusion, it would be the right approach to abstain from using and incentivizing this product, until its benefits and harms are set out clearly, by considering its potential side effects.

Recent advances in the management of hepatocellular carcinoma.

Abstract: Purpose: The fifth most common cancer of the gastrointestinal system is liver cancer. It is also one of the most common cancers worldwide. The available treatment options include surgery, percutaneous ablation, and liver transplantation. Some of the latest modalities for the management of hepatocellular carcinoma (HCC) are radiofrequency ablation, trans-arterial chemoembolization, radioembolization and systemic targeted agents like sorafenib. The process of choice of a particular treatment modality in HCC depends on the tumor stage, patient performance status and liver function reserve. In the recent past with progress in research, the short-term survival of HCC has improved but recurrent disease remains a fundamental problem as the pathogenesis of HCC is a multistep and complex process. The present review is focused on recent advances in the management of HCC. This review will also provide an insight on the upcoming latest modalities including the emerging role of hepatoma-derived growth factor (HDGF) overexpression in liver fibrosis and carcinogenesis.

Survival and prognostic factors in patients with brain metastasis: Single center experience.

Abstract: Purpose The purpose of this study was to evaluate the clinical status, prognostic factors and treatment modalities affecting survival in patients with brain metastasis. We aimed to evaluate the whole brain radiation therapy (WBRT) outcomes of patients with brain metastasis in our center. Methods Clinical data of 315 patients referred to our center between 2004 and 2014 with metastatic brain cancers were collected and analysed for possible relationships between survival time, age, gender, Karnofsky performance status (KPS), recursive partitioning analysis (RPA), primary tumor, number of brain lesions, surgery, radiation therapy scheme, extracranial metastatic status and primary disease control status. Results The average patient age of onset was 58 years. The primary tumor site was lung (68%), breast (12%), melanoma (4%), colorectal (1.6%), sarcoma (1.3%) and unknown primary disease (4.4%). The rest of the patients had other primary sites. Eighty four (26.6%) patients had single brain metastasis, 71 (22.5%) had 2 or 3 lesions, and 159 (50.4%) patients had more than 3 lesions. Leptomeningeal involvement was seen in combination of paranchymal involvement in 11 (3.5%) patients. Fifty patients had undergone surgical resection. WBRT was delivered to all of the patients. Median overall survival was 6.7 months (95% CI, 5.80-7.74). Median overall survival of patients treated with combination of surgery and WBRT was significantly better compared with those treated with WBRT alone (13.5 vs 5.5 months, p=0.0001). One- and 2- year survival was 17 and 4.7%, respectively. Conclusions The present study concludes that brain metastasis is common in cancer patients. The best overall survival was obtained by surgery+NBRT in good-condition patients. Treatment should be tailored on an individual basis to all these patients.

Ablation of the locally advanced pancreatic cancer: An introduction and brief summary of techniques.

Abstract: Pancreatic ductal adenocarcinoma is a lethal and late presenting malignancy with dismal survival rates. An estimated total of 330,000 people died from this malignancy in 2012. Although there have been improvements in diagnostic and treatment methods, the survival of late stage pancreatic cancer has not shown significant improvement in the past 4 decades. Multiple treatment approaches are available including chemotherapy, radiotherapy, and immunotherapy, but to this day surgical resection remains the only curative treatment option. Ablative techniques use various forms of energy to cause local tissue destruction through necrosis or apoptosis. They are relevant in pancreatic ductal adenocarcinoma as they are a treatment option in non-resectable tumors where their use ranges from symptom control to reducing tumor size for resection. In this narrative review we have grouped and outlined the various ablative methods, classifying them into thermal (Radiofrequency ablation, Microwave ablation, High Intensity Focused Ultrasound ablation, Cryoablation), and non-thermal ablative methods (Irreversible Electroporation (NanoKnife®), Photodynamic Therapy). This is followed by a description and review of the available evidence on survival and complications for each of these ablative methods. According to the literature, thermal ablative methods appear to be more accessible but are implicated with more complications than non thermal ablative methods which show the most promise.

Overview on the current status of virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part I.

Abstract: Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anti- cancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery. A number of recent successful drugs have in part or in whole emerged from a structure-based research approach. Many advances including crystallography and informatics are behind these successes. Increasing insight into the genetics and molecular biology of cancer has resulted in the identification of an increasing number of potential molecular targets, for anticancer drug discovery and development. These targets can be approached through exploitation of emerging structural biology, "rational" drug design, screening of chemical libraries, or a combination of these methods. The result is the rapid discovery of new anticancer drugs. In this article we discuss the application of molecular modeling, molecular docking and virtual high-throughput screening to multi-targeted anticancer drug discovery. Efforts have been made to employ in silico methods for facilitating the search and design of selective multi-target agents. These computer aided molecular design methods have shown promising potential in facilitating drug discovery directed at selective multiple targets and is expected to contribute to intelligent lead anticancer drugs.

Laparoscopic versus open hepatectomy for hepatocellular carcinoma: long-term outcomes.

Abstract: Purpose This study compared the longterm survival outcomes of patients with hepatocellular carcinoma (HCC) who underwent laparoscopic hepatectomy with those who were subjected to open hepatectomy. Methods This was a retrospective, case-control study; patients in the 2 groups were matched according to age, sex, body mass index (BMI), liver function, underlying liver disease, American Society of Anesthesiologists (ASA) score, tumor location and type of resection. A total of 118 patients (laparoscopy, N = 59; open, N = 59) were assessed. Results Patient characteristics did not differ between the groups. Postoperative 30-day complication rates did not differ between the groups. Pathological data did not differ between the two groups. The 5-year overall survival (OS) and disease-free survival (DFS) were not different between the laparoscopy and open groups. The laparoscopic approach was not an independent risk factor for tumor recurrence or mortality compared with the open approach. Conclusion We found no differences in the oncologic outcomes between laparoscopic and open hepatectomy groups, suggesting that laparoscopic hepatectomy for HCC is a safe and effective option that does not increase the risk of serious complications.

Laparoscopic versus open hepatectomy for elderly patients with liver metastases from colorectal cancer.

Abstract: PURPOSE To date, it is unclear whether laparoscopic hepatectomy (LH) is a suitable treatment for elderly patients (aged ?65 years) with liver metastases from colorectal cancer. The aim of the present study was to clarify the value of LH in the elderly using the propensity score matching method. METHODS Data from 385 elderly patients who underwent hepatectomy for liver metastases from colorectal cancer at our institution between January 2008 and January 2016 were prospectively collected. Propensity score matching was applied at a ratio of 1:1 to compare LH and open hepatectomy (OH) groups. The short- and long-term outcomes were compared between the matched groups. RESULTS The LH group had significantly less blood loss than the OH group. The postoperative length of hospital stay was shorter in the LH group than in the OH group: however, no significant intergroup differences were found in morbidity and mortality. Furthermore, the 5-year overall (OS) and disease-free survival (DFS) rates were similar between the two groups. CONCLUSION LH for elderly patients with liver metastases from colorectal cancer was feasible and safe with acceptable oncologic outcomes. Therefore, patient age alone should not be considered as a contraindication when deciding between LH and OH as treatment options.

The mean platelet volume may predict the development of isolated bone metastases in patients with breast cancer: a retrospective study of the Young Researchers Committee of the Turkish Oncology Group (TOG).

Abstract: PURPOSE To determine the predictive value of the mean platelet volume (MPV) and the MPV/platelet count ratio on the development of isolated bone metastasis in patients with breast cancer. METHODS A total of 121 previously untreated female patients with isolated bone metastases from breast cancer (group 1) were included in this retrospective cohort study. The patients enrolled in this study had similar age, biological subtypes, and duration of follow-up after diagnosis. Group 1 was compared with both 71 previously untreated women with breast cancer with no metastases at all (group 2) and 39 healthy women (group 3). Demographic data, laboratory tests and histological features of all of the patients in groups 1 and 2 were recorded and the study variables from each of the three groups were compared. RESULTS In group 1, the cut-off value (9.2 fL) for the MPV was determined and patients were stratified into 4 subgroups. The MPV was higher in group 1 than in either group 2 or group 3. Group 1 patients had a MPV of 8.8±3.1 fL (mean 5.1, range: 6.1-15.6) and the cut-off value for MPV was 9.2 fl. For patients in group 1, the MPV distribution was stratified into 4 groups as follows: group A included MPV values 10.06 fL. MPV and the presence of lymphovascular invasion were found to be independent risk factors for the development of isolated bone metastases. CONCLUSION We concluded that MPV can be used to predict the development of isolated bone metastases.

Biological characteristics of CCN proteins in tumor development

Abstract: The extracellular membrane (ECM) is no longer regarded as inert, rather it has multiple versatile physiologic functions. Its diverse composition is implicated in each step of cancer progression including inflammation, angiogenesis, tumor invasion and metastasis. In addition to structural proteins, the ECM also contains a family of non-structural proteins called matricellular proteins. The six secreted CCN proteins, which belong to the matricellular protein family, include the following: Cyr61 (CCN1), CTGF (CCN2), Nov (CCN3), WISP- 1 (CCN4), WISP-2 (CCN5) and WISP-3(CCN6). These proteins are capable of modulating a variety of biological processes in health as well as in disease conditions. In tumor development and in tumor microenvironment, CCN proteins can influence multiple facets of pathophysiological processes including cellular proliferation, invasion and metastasis. This review has attempted a cohesive look at the CCN family protein functions in a tumor-specific manner.

A propensity score-matched case-control comparative study of laparoscopic and open gastrectomy for locally advanced gastric carcinoma.

Abstract: PURPOSE The aim of this study was to compare the surgical and long-term outcomes of laparoscopic and open gastrectomy with radical intent for locally advanced gastric carcinoma in case-controlled patient groups using the propensity score. METHODS Between January 2009 and December 2014, 389 patients who underwent gastrectomy with radical intent for locally advanced gastric carcinoma were enrolled. These patients were divided into two groups according to the method of operation: the laparoscopy group (patients who underwent laparoscopic gastrectomy) and the open group (patients who underwent open gastrectomy). To correct different demographic and clinical factors in the two groups, a propensity score matching was used at a 1:1 ratio, and, finally, 184 patients were enrolled in this study, 92 patients in each group. Preoperative characteristics, surgical results, and long-term results were analyzed. RESULTS Preoperative baseline variables were well balanced in both groups. There were no differences of the extent of surgery between the two groups. With the exception of shorter postoperative hospital stay and less blood loss in the laparoscopy group as compared with the open group, there were no significant differences in surgical, pathological, and long-term outcomes. The 5-year overall survival rates were 57% in the laparoscopy group and 50% in the open group (p=0.606). The 5-year disease-free survival rates were 48% in the laparoscopy group and 42% in the open group (p=0.515). CONCLUSION Laparoscopic gastrectomy for locally advanced gastric carcinoma is safe, and long-term outcomes were comparable to those who underwent open resection.

Resveratrol in lung cancer- a systematic review.

Abstract: Purpose Resveratrol, a phytochemical known for its anti- oxidative properties has been explored worldwide for anticancer potential. We performed this systematic review and meta-analysis in order to register the efficacy of resveratrol against lung carcinogenesis. Methods We searched PubMed for preclinical studies reporting efficacy of resveratrol alone or in combination with drugs like curcumin, cisplatin etc. against lung carcinogenesis. Results The primary outcome of eligible studies included change in overall tumor incidence as well as tumor size. In all of the above studies involving either animal models or in vitro cancer cell experiments a statistically significant reduction in tumor incidence emerged as compared with the control groups, yielding a relative risk reduction of 0.64 (p=0.002). This meta- analysis confirmed the potential of resveratrol against lung carcinogenesis. Conclusion It can be concluded that resveratrol holds a good potential for future use as a highly efficient therapeutic agent to deal with deadly lung carcinogenesis.

Laparoscopic total gastrectomy compared with open resection for gastric carcinoma: a case-matched study with long-term follow-up.

Abstract: PURPOSE This study was designed to compare the long-term outcomes of patients with gastric carcinoma after open or laparoscopic total gastrectomy. METHODS A case-matched controlled prospective analysis of 136 patients who underwent laparoscopic total gastrectomy for stage I-III gastric carcinoma from 2007 to 2014 was performed. Patients who at the same period underwent open total gastrectomy were matched to the laparoscopy group at the ratio of 1:1 for comparison. The perioperative clinical outcomes, postoperative pathology, and survival were compared between the 2 groups RESULTS The patient characteristics between the two groups were comparable. Laparoscopic resection resulted in less blood loss, shorter postoperative hospital stay, and longer operating time. The two groups had similar complication rates. Pathological data were similar for both procedures. Cumulative incidence of recurrence, disease-free, or overall survival rates were statistically similar. CONCLUSION This study showed that laparoscopic total gastrectomy for gastric carcinoma is acceptable in terms of short-term clinical outcomes and long-term survival results.

Proliferation inhibition and apoptosis of breast cancer MCF-7 cells under the influence of colchicine.

Abstract: Purpose This study was designed to explore the effect of colchicine on the proliferation and apoptosis of Breast Cancer Michigan Cancer Foundation - 7 (MCF-7) cells. Methods The experiment was conducted at the University Laboratory of East Provincial Hospital in April, 2015. The first inhibitory effect of colchicine on breast cancer MCF-7 cells was observed by MTT (3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide) assay, and then the effect of colchicine on apoptosis of breast cancer MCF-7 cells was measured by flow cytometry. Results The colchicine's inhibitory effect on breast cancer MCF-7 cells gradually increased with increasing concentration and longer exposure time. Breast cancer MCF-7 cells showed different levels of apoptosis with different colchicine concentrations at 24th, 48th and 72nd hrs, and the apoptosis rate tended to be higher with increasing concentration and prolonged exposure time. Conclusion All the findings suggest that colchicine is able to inhibit proliferation of breast cancer MCF-7 cells and induce cell apoptosis, and the intensity of the effect was associated with dosage and time.

Selective cytotoxic effect of Rhododendron luteum extract on human colon and liver cancer cells.

Abstract: Purpose The genus Rhododendron is distributed entirely in the world with the exception of South and Central America and Africa, growing in a large diversity of climatic conditions This genus is a rich source of phenolic compounds, especially flavonoids, essential oils, chromones, terpenoids, and steroids It has many biological properties such as antioxidant, anti-inflammatory, antiviral, antibacterial, anticancer, antidiabetic, immunomodulatory, cardioprotective and hepatoprotective among others due to their polyphenolic constituents The objective of the current study was to evaluate the antioxidant properties and cytotoxic activity of dimethyl sulfoxide extract of flowers of Rhododendron luteum (DEFR) for the first time Methods The total polyphenolic contents (TPC), total flavonoid contents (TFC) and ferric reducing antioxidant power (FRAP) of the extract were evaluated using spectrophotometric procedures The cytotoxic activity of the extract on three cancers (human breast, colon and liver carcinoma) and human foreskin fibroblast cells was determined using the MTT assay Results TPC and FRAP values were found 542±038 mg gallic acid equivalents and 1642±177 mg trolox equivalents per to g sample, respectively Rluteum extract exhibited selective cytotoxicity against colon and liver cancer cells compared to normal fibroblast cells, while this selective cytotoxicity was not observed in breast cancer cells Conclusion Our results demonstrate that the Rhododendron luteum may be a great source of antioxidant and antitumor natural agents due to their capability of decreasing cancer cells proliferation

New evidence of TERT rs2736098 polymorphism and cancer risk: an updated meta-analysis.

Abstract: Purpose Previous meta-analyses didn't suggest any significant association between TERT rs2736098 polymorphism and overall cancer risk, and the existing evidence lacks statistical power to draw a convincing conclusion. Methods Herein we performed an update meta-analysis to re-evaluate the association between rs2736098 polymorphism and the risk of overall cancer with all the case-control studies published before March 2015 according to PubMed and Embase databases. Results A total of 19 case-control studies were included in this analysis. We found that variant genotypes of rs2736098 (GA/AA) were significantly associated with an increased risk of overall cancer (GA/AA vs GG: OR=1.14; 95% CI=1.04-1.25). Additionally, the association was more significant in Asians (OR=1.20; 95% CI=1.07-1.34), while in subsequent analyses stratified by cancer type, the variant rs2736098 was definitely associated with increased lung cancer (OR=1.18; 95% CI=1.07-1.29) and hepatocellular carcinoma risk (OR=1.38; 95% CI=1.20-1.59). Conclusion These findings provided further evidence that TERT rs2736098 variant may modify the susceptibility to cancer.

Tumor deposits: Prognostic significance in gastric cancer patients.

Abstract: Purpose Tumor deposits (TDs) are defined as satellite peritumoral nodules in the peritumoral adipose tissue of a primary carcinoma without histologic evidence of residual lymph node in the nodule. We aimed to investigate the relation between TDs and clinicopathological characteristics of gastric cancer and to evaluate the effect of TDs on prognosis. Methods One hundred and seven non-metastatic gastric cancer patients were enrolled. The relationships between positive and negative TDs with respect to clinicopathological characteristics, as well as disease free survival (DFS) and overall survival (OS), were analyzed. Results TDs were detected in 28 patients (26.2%). Advanced pT stage and pN stage were significantly higher in TDs-positive compared to TDs-negative patients (p=0.015 and p=0.037, respectively). No significant differences were identified between the groups in other clinicopathological variables such as gender, lymphovascular and perineural invasion. Recurrence and mortality rates were higher in the TDs-positive patients during follow-up of both groups (22/78.6% vs 38/48.1%, p=0.010 for relapse; 20/71.4% vs 3/38%, p=0.005 for mortality). The univariate analysis demonstrated shorter DFS and OS for TDs-positive compared to TDs-negative patients. In multivariate analysis, TDs-positive patients had 1.75-fold higher likelihood to develop recurrence, while the likelihood of death increased 1.99-fold (p=0.041 and p=0.020, respectively). Conclusion TDs-positive gastric cancers demonstrate a more aggressive clinical course compared to TDs-negative. More effective treatment methods should be necessary for management of this subgroup of gastric cancer.

Expression of Nestin and CD133 in serous ovarian carcinoma.

Abstract: Pupose: Nestin and CD133 are regarded as putative markers of cancer stem cells (CSCs) and related to poor prognosis in various cancer sites. Since few studies have focused on their role in ovarian cancer, we aimed to investigate their predictive value and association with neoangiogenesis. Methods Immunohistochemical analysis for nestin and CD133 was performed on 85 serous ovarian carcinoma tumor samples using tissue microarray technique. Nestin immunoreactivity was detected in both tumor and endothelial cells, whilst CD133 was only identified in tumor cells. CD34 endothelial expression was used to assess intratumor microvessel density (MVD). Results Of the tissue samples 49.4% were nestin-positive and 24.7% were positive for CD133. In both univariate and multivariate analysis nestin or CD133 expressions in tumor cells were not significantly associated with clinicopathological parameters (age, serum CA125, peritoneal carcinomatosis, malignant ascites, tumor grade). However, in multivariate analysis nestin expression in tumor cells proved to be an independent prognostic factor, associated with poorer survival and time to progression (p=0.025 and p=0.05, respectively). This has not been achieved for CD133. Furthermore, a significant concordance between nestin endothelial expression (nestin-determined MVD) and CD34-determined MVD was achieved. Conclusion In addition to the well-known clinicopathological characteristics, tumor expression of nestin might be a valuable prognostic factor for survival in patients with advanced ovarian cancer. With regard to its endothelial expression, nestin might be as reliable as CD34 for quantifying tumor angiogenesis. Further investigation is justified in order to better clarify the role of these biomarkers.

Correlation of p210 BCR-ABL transcript variants with clinical, parameters and disease outcome in 45 chronic myeloid leukemia patients.

Abstract: Purpose The aim of this study was to search the BCR/ABL 1 fusion gene in 45 chronic myeloid leukemia (CML) Syrian patients using nested reverse transcription polymerase chain reaction (RT-PCR) and compare our results with those of conventional cytogenetics and molecular cytogenetics methods. Methods 45 bone marrow or peripheral blood samples from untreated CML patients in chronic phase (CP) were obtained at diagnosis, and analyzed by nested RT-PCR, conventional cytogenetics and molecular cyto-genetics methods. Results 45 patients examined were positive for some type of BCR/ABL1 fusion gene rearrangement. Out of 45 studied CML patients, 23 (51.1%) expressed b3a2 fusion transcript, 21 (46.7%) b2a2 transcript, and 1 (2.2%) a rare b2a3 transcript. No patient co-expressed both b3a2/b2a2 types. Conclusions The distribution BCR-ABL1 transcript types found in Syria were similar to that of Indian Far-Eastern, African or European populations and the M-BCR rearrangement types were not dependent on white blood count (WBC), platelet count, hemoglobin level or gender of the patients. Overall, we could show that patients with b3a2 rearrangements were younger than patients with b2a2 transcripts, thus our young patients may have a worse prognosis.

Sensitizer drugs for the treatment of temozolomide-resistant glioblastoma.

Abstract: Purpose Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor. Despite maximal cytoreductive surgery followed by chemoradiotherapy the prognosis is still poor. Although surgery and radiotherapy may have reached maximal effectiveness, chemotherapy has the potential to improve survival. The aim of this study was to evaluate in vitro the antitumor efficacy of tamoxifen (TAM), raloxifen (RAL), pyrimethamine (PYR) and alphanizomenon flos-aquae (AFA) in combination with temozolomide (TMZ) plus ionizing radiation against cultured glioblastoma stem-like cells and primary glioblastoma cells , as possible way to increase the treatment options in patients with therapy-refractory GBM. Methods Stem-like tumor cells and glioblastoma cells isolated from two GBM biopsies were established by cell proliferation assays. TAM, RAL, PYR and AFA were added prior to TMZ and ionizing irradiation. Results All tested drugs enhanced the cytotoxic effect of TMZ and sensitized cancer cells to radiotherapy as demonstrated by MTT assay and different staining reagents (TMRE, Hoechst dye and Annexin V) used for monitoring of several events in apoptosis. Conclusion The administration of certain selective estrogen receptor modulators (SERMs) (TAM and RAL), PYR and AFA before conventional postoperative chemo radiotherapy for glioblastoma might increase therapy efficiency compared to standard oncological treatment. These results need to be extended in vivo on laboratory animals in order to test the encouraging results obtained in vitro.

Prognostic indicators following curative pancreatoduodenectomy for pancreatic carcinoma: A retrospective multivariate analysis of a single centre experience.

Abstract: PURPOSE Survival after curative resection of pancreatic, ampullary and lower common bile duct cancer remains very poor The aim of this study was to assess important prognostic factors in patients with resectable pancreatic cancer METHODS From 2006 to 2010, 156 patients underwent pancreatoduodenectomy (PD) for malignancies of pancreatic, ampullary or lower common bile duct in our institution Based on the inclusion criteria 101 patients were selected in our retrospective statistical analysis Of these 101 cases of malignancies, 654% were located in the pancreatic head, 188% in the ampulla and 158% in the lower bile duct 485% of patients underwent classical PD, and 515% pylorus-preserving pancreatoduodenectomy (PPPD) Clinical and pathological data were collected, Kaplan-Meier method and Cox proportional hazard models were used to evaluate prognostic factors RESULTS Multivariate analysis revealed that blood transfusion, vascular invasion, T4 vs T1 stage, and R0 resection margins were significant negative predictors of survival Conversely, ampullary (vs pancreatic ductal) and adjuvant chemotherapy were significantly associated with longer survival Lymph node ratio (LNR), in all its forms, was not found to have a significant effect on survival For all patients, tumor grading (p=0042), resection margins (p=0004), T stage (p=0001), perineural invasion (p=0029), vascular invasion (p=0007) and age >65 years (p=0009) were factors that impacted survival CONCLUSION Surgical resection margins, tumor grade, T stage, perineural invasion, vascular invasion, age >65 and adjuvant chemotherapy are the strongest predictors of survival after surgical resection of pancreatic, ampullary and lower common bile duct cancer In this series, lymph node ratio did not impact survival

Anticancer activity of Honokiol against lymphoid malignant cells via activation of ROS-JNK and attenuation of Nrf2 and NF-κB.

Abstract: Purpose To evaluate the effect of Honokiol (HK) in the ROS-JNK pro-apoptotic pathway and NF-κB, Nrf2 anti-apoptotic pathways, in order to seek a possible explanation for its anticancer efficacy. Methods The Raji and Molt4 cell lines were utilized for the determination of anticancer activity against lymphoid malignant cells. BALB/C nude mice, weighing 18-20g each and aged 4-5 weeks, were procured from the central animal house facility. For establishing non-Hodgkin lymphoma in BALB/C, the nude mice were subcutaneously administered 1×10(7) Raji cells, suspended in 0.2 mL sterile PBS on the back. The mice were then randomly divided into 3 groups (6 mice in each group). HK cytotoxicity was determined using the colorimetric MTT assay. Results In colorimetry-based MTT assay, the cytotoxicity of HK was determined at different time intervals, in lymphoid malignant Raji and Molt4 cell lines. HK exhibited prominent cytotoxicity against Raji cell lines with IC50 of 0.092 ± 0.021 μM. In Molt4 cells, the administration of HK caused significant cytotoxicity with IC50 of 0.521 ± 0.115 μM. The treatment of HK caused significant increase in the activity of reactive oxygen species (ROS) in Raji cells at various time intervals. Moreover, the level of NF-κB was significantly reduced in the presence of HK, which could be easily understood by a decreased level of p-65. Furthermore, in the presence of ROS inhibitor NAC (10mM) for 24 hrs, the JNK pathway was markedly activated, together with inhibition of NF-κB activity and a reduced level of Nrf2 expression. To further confirm the in vitro results by in vivo activity, HK was observed to inhibit the proliferation of Raji cells in vivo, which might be attributable to its inhibitory effect against the progression of the tumor (p Conclusion The present study suggests that HK causes considerable induction of apoptosis in lymphoid malignant cells, both in vitro and in vivo, whereas the generation of ROS might serve as an underlying mechanism for inducing apoptosis.

The effect of Guidelines in surgical decision making: The paradigm of hepatocellular carcinoma.

Abstract: It is not inconceivable to envision surgeons, offering extended liver resection in patients beyond the Barcelona Clinic Liver Cancer (BCLC) staging system criteria with intermediate/advanced hepatocellular carcinoma (HCC), to be found negligent since extensive liver resection is correlated with increased morbidity compared to conservative or palliative treatment. Given that no other classification system than BCLC has been adopted widely for HCC staging and treatment, a revision of the BCLC algorithm and clinical guidelines should be tailored using new molecular and clinical treatment algorithms, as well as including patient's preferences.

Correlations of magnetic resonance, perfusion-weighed imaging parameters and microvessel density in meningioma.

Abstract: Purpose To investigate the correlations of magnetic resonance, perfusion-weighed imaging (PWI) parameters and microvessel density (MVD) in meningioma. Methods 48 patients with pathologically confirmed meningioma (grade I, 38 cases; grade II+III, 10 cases) completed preoperative routine magnetic resonance imaging (MRI) and PWI. The cerebral blood volume (CBV) map of solid tumor region and the mean of maximum relative cerebral blood volume (rCBV) were then calculated. Immunohistochemical staining was performed in all specimens to measure the MVD. Results On the CBV map, benign meningiomas showed a high perfusion signal, while malignant meningiomas exhibited a slightly higher one. The rCBV of benign meningiomas was 9.61±4.76, which was significantly higher than 3.61±0.25 of malignant meningiomas (t=7.165, p=0.000). The MVD of benign meningioma strips was 21.16 ± 11.32, which was also significantly higher than 10.71 ± 5.53 strips of malignant meningiomas (t=2.325, p=0.026). The correlation analysis showed that the mean of maximum rCBV and MVD of meningiomas had significant positive correlations (r=0.718, p=0.000). Conclusions The CBV map of benign meningiomas is different to that of malignant meningiomas, and the mean of maximum rCBV and MVD have significant positive correlations.