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   2016| October-December  | Volume 12 | Issue 4  
    Online since February 7, 2017

 
 
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REVIEW ARTICLES
Palbociclib: A new hope in the treatment of breast cancer
R Priyadharsini Palanisamy
October-December 2016, 12(4):1220-1223
DOI:10.4103/0973-1482.168988  PMID:28169231
Breast cancer being one of the common cancers has high morbidity and mortality. Despite the conventional treatment, the burden of the disease increases year after year. There is a need for newer drugs that target the different mechanisms in the pathogenesis. The interaction of cyclins with cyclin dependent kinases (CDKs) plays a major role in the abnormal cell cycle in cancer and it is considered to be an important target. Palbociclib is a CDK inhibitor currently approved for the treatment of breast cancer. The preclinical studies with breast cancer lines were sensitive to palbociclib and the clinical trials phase I, phase II (PALOMA 1), and phase III (PALOMA 2, 3, PENTELOPE, PEARL) showed that the drug was efficacious when combined other conventional drugs for breast cancer. Palbociclib was also been tested in various other germ cell tumors, melanoma, multiple myeloma, glioblastoma multiforme etc., The major adverse effect of the drug includes hematological toxicity mainly neutropenia, gastrointestinal adverse effects.
  3,169 248 -
E-JCRT CORRESPONDENCE
A case of unilateral atypical orofacial pain with Eagle's syndrome
GV Sowmya, Mohit Pal Singh, BS Manjunatha, Prashant Nahar, Madhusudan Astekar
October-December 2016, 12(4):1323-1323
DOI:10.4103/0973-1482.144558  PMID:28169247
Eagle's syndrome is not an uncommon condition, but less known to physicians, where an elongated styloid process or calcified stylohyoid ligament compresses the adjacent anatomical structures leading to orofacial pain. Diagnosis is made with appropriate radiological examination. Nonsurgical treatment options include reassurance, analgesia, and anti.inflammatory medications; and the surgical option includes a transoral or external approach. Here, we present a case report of a male patient, of age38 years, with a chief complaint of unilateral atypical orofacial pain on the right side of his face radiating to the neck region, for the last two months.
  2,193 199 -
REVIEW ARTICLES
Adjuvant treatment for Stage I seminoma: Why radiotherapy is better than carboplatin
Prahlad H Yathiraj, Krishna Sharan, Donald J Fernandes, MS Vidyasagar
October-December 2016, 12(4):1216-1219
DOI:10.4103/0973-1482.176171  PMID:28169230
Adjuvant treatment options for Stage I seminoma include active surveillance, chemotherapy, and radiotherapy. Active surveillance may not be ideal for the average Indian patient. Of the two accepted adjuvant therapy options, namely single-dose carboplatin chemotherapy and radiotherapy to the retroperitoneal nodes, though it intuitively appears more appealing, a deeper review reveals the potential drawbacks of chemotherapy. This article highlights the misconceptions regarding carboplatin and provides reasons for an argument why radiotherapy is better when a patient with Stage I seminoma chooses to undergo adjuvant treatment.
  1,770 162 -
ORIGINAL ARTICLES
Salvage stereotactic radiosurgery for recurrent glioblastoma multiforme with prior radiation therapy
Douglas E Holt, Mark E Bernard, Kimmen Quan, David A Clump, Johnathan A Engh, Steven A Burton, Dwight E Heron
October-December 2016, 12(4):1243-1248
DOI:10.4103/0973-1482.199537  PMID:28169234
Background: Glioblastoma multiforme (GBM) carries a poor prognosis with high recurrence rates. Salvage stereotactic radiosurgery (SRS) may be an effective treatment option. Methods: We retrospectively reviewed 34 patients (41 lesions) treated with salvage SRS for recurrent GBM between 2004 and 2012. Initial surgical treatments were gross total resection (58%), subtotal resection (STR) (24%), and biopsy (18%). All patients were treated with prior radiation therapy. Recurrent disease was treated with salvage SRS with a median dose and fractions of 23.4 Gy (range, 12–30) and 3 (range, 1–3), respectively. Cox proportional hazards regression was conducted to establish predictive factors (P ≤ 0.05) Results: Median follow-up from salvage SRS was 10.8 months (interquartile range [IQR], 7.0–15.6). The median time from initial radiation therapy to salvage SRS was 13.7 months (IQR, 2.9–25.0). The 6- and 12-month overall survival from salvage SRS were 84.9% and 42.5%, respectively. On univariate analysis, STR was associated with inferior survival from salvage SRS (P ≤ 0.05). The 6- and 12-month local control (LC) estimates were 63.1% and 16.4%, respectively. On univariate analysis, higher biological effective dose and prior temozolomide were associated with superior LC. Concerning toxicity, there were 4 (12%) grade 2 and 1 (3%) grade 3 adverse events within this patient series. No grade 4 or grade 5 toxicities were observed. Conclusion: Our outcomes suggest that SRS is a feasible treatment option with acceptable salvage survival rates, given the poor prognosis of this disease.
  1,579 142 -
REVIEW ARTICLES
Membrane-bound versus soluble major histocompatibility complex Class I-related chain A and major histocompatibility complex Class I-related chain B differential expression: Mechanisms of tumor eradication versus evasion and current drug development strategies
PK Suresh
October-December 2016, 12(4):1224-1233
DOI:10.4103/0973-1482.176169  PMID:28169232
Major histocompatibility complex Class I-related chain A/chain B (MICA/MICB) is stress-inducible, highly polymorphic ligands whose expression at the transcript level has been detected in all tissues except the central nervous system. However, their restricted protein expression is due to their regulation at the posttranslational level. Its levels are elevated in virally infected and neoplastically transformed cells. Membrane expression of this NKG2DL marks the aberrant cells for elimination by those immune effector cells that express the cognate NKG2D receptor. Among the evasion strategies developed by tumors, the metalloprotease-dependent shedding of MICA/MICB from tumors (either the free or the exosome form) can contribute to the inhibition of cytolysis by the immune effector cells (all NK cells, most NKT cells; γδ CD8+ T cells and αβ CD8+ T cells, as well as some αβ CD4+ T cells). There are micro-RNA clusters that regulate surface expression and shedding. Polymorphic variants can be used as susceptibility/associative markers and can also possibly be used to correlate with tumor survival as well as staging/grading of tumors. Variations in the expression level require quantification of this marker for diagnostic/prognostic and therapeutic purposes. Mechanism-based studies would provide a better tumor-specific understanding of their relative roles in the processes of tumor cell elimination versus growth and progression. Last but not least, conventional, interlaboratory validated assays (for, e.g., antibody-based methods) should be replaced by robust, reproducible, feasible biophysics-based methods using tumor biopsies. Further, correlative DNA polymorphism-based studies can be done using biological fluids (for, e.g., human saliva) that can be sampled by minimally invasive means.
  1,540 110 -
ORIGINAL ARTICLES
Evaluating the effects of ellagic acid on pSTAT3, pAKT, and pERK1/2 signaling pathways in prostate cancer PC3 cells
Elaheh Eskandari, Esfandiar Heidarian, Sayed Asadollah Amini, Javad Saffari-Chaleshtori
October-December 2016, 12(4):1266-1271
DOI:10.4103/0973-1482.165873  PMID:28169238
Objective: One of the most common malignancies among men is prostate cancer. Ellagic acid (EA), a polyphenol antioxidant, has many pharmacological actions, especially anticancer effects. The purpose of this study was to evaluate the effect of EA treatment on interleukin-6 (IL-6) gene expression, cell viability, IL-6 secretion, phosphorylated STAT3, ERK, and AKT cellular signaling proteins in human prostate cancer cells (PC3). Materials and Methods: The cytotoxic effects of the EA (0-100 µM) on PC3 cells were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. IL-6 gene expression was down, using real-time quantitative polymerase chain reaction. The cellular concentration of phosphorylated ERK1/2, AKT, and STAT3 signaling pathways was assessed by Western blotting technic. Results: EA treatment of PC3 cells resulted in a reduction of cell viability and phosphorylated STAT3, ERK, and AKT signaling proteins after 72 h in a dose-dependent manner. IL-6 gene expression and IL-6 levels significantly increased (P < 0.05) in a dose-dependent pattern in treated PC3 with EA. Thus, these data suggested the essential role of signaling proteins in EA-mediated anti-proliferation of PC3 cells. Conclusions: Our finding shows that EA can be considered as a potent agent that decreases cell proliferation through a reduction of phosphorylated STAT3, ERK, and AKT cellular signaling proteins.
  1,357 109 -
Enhanced cytotoxic activity of endophytic bacterial extracts from Adhatoda beddomei leaves in A549 lung cancer cell lines
Y Swarnalatha, Bhaswti Saha
October-December 2016, 12(4):1284-1290
DOI:10.4103/0973-1482.161928  PMID:28169241
Aim of the Study: The current study is aimed to isolate and study the efficacy of the anticancer activity of endophytic bacteria from adhatoda beddomei leaves. Endophytic bacteria, microorganisms can found in the plant tissues, like leaves, branches and roots and able to produce various novel secondary metabolites for the medicinal applications. Methodology: Endophytic bacteria were isolated from the leaves of the adhatoda beddomei leaves. The extract from the culture was tested for the cytotoxicity in A549 cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay, dual staining and nuclear staining. Results: The expression of the apoptotic and proliferative genes were assessed with the reverse transcriptase polymerase chain reaction (RT-PCR) comparing with the control gene. The inhibitory concentration (IC50) of the bacterial extract was found to be 43.97 μg/ml. With the dual staining the apoptotic cell percentage was significantly increased (P < 0.001) and with the 40μg/ml and 80μg/ml concentration the apoptotic percentages observed as 67% and 89% respectively. Similar concentrations were used for the nuclear fragmentation (PI) and the cell cycle analysis (FACS) using WinMDI 2.9 software. During cell cycle analysis the accumulation of the cells at G0-G1 stage was observed with increasing concentrations of the chi-alg encophytic bacterial extract nanoparticles. Finally the proapoptotic and proliferative gene expression for the bax, Bcl-2 and caspase was significantly regulated (P < 0.01; P < 0.05). The Bax and Caspase were up-regulated and Bcl-2 was down regulated. Conclusion: The results conclude that enophytic bacterial extract possess good cytotoxic activity.
  1,202 130 -
Synergistic induction of apoptosis in B-cell chronic lymphocytic leukemia cells after treatment with all-trans retinoic acid in combination with interleukin-21 and rituximab
Kazem Abbaszadeh-Goudarzi, Fazel Shokri, Mostafa Hosseini, Farhad Jadidi-Niaragh, Ghasem Ghalamfarsa, Ali Akbar Saboor-Yaraghi
October-December 2016, 12(4):1278-1283
DOI:10.4103/0973-1482.184522  PMID:28169240
Aim: B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world and characterized by the progressive expansion of malignant B lymphocytes in peripheral blood. In spite of advances in sciences to recognize the number of effective agents for the treatment of chronic lymphocytic leukemia (CLL), this leukemia is thought as incurable one. Introducing a new therapy that has a direct effect on B-CLL lymphocytes and no cytotoxic effects on the other cells is a great wish. Materials and Methods: Twenty-one patients with B-CLL were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated from patients' blood samples and were further treated with all-tans retinoic acid (ATRA), interleukin (IL-21), and rituximab at concentrations of 30 ng/ml, 25 ng/ml, and 4 μg/ml, respectively. ATRA, IL21, and rituximab were used alone or in various combinations and their effects on apoptosis were measured using annexin V-fluorescein isothiocyanate apoptosis detection kit. Result: Treatment of the patients' cells with IL21 and rituximab showed a synergistic effect on the induction of apoptosis, in comparison with untreated CLL cells (P < 0.05). The induction of apoptosis by ATRA in combination with IL21 and rituximab were significantly increased compared to untreated CLL cells as a negative control (P < 0.01). Conclusion: Treatment of patients' PBMCs by ATRA in combination with IL21 and rituximab and also IL21 in combination with rituximab showed synergistic induction of apoptosis compared to untreated CLL cells as a negative control (P < 0.01). It seems that ATRA in combination with IL21 and rituximab activate different pathways of apoptosis (extrinsic pathway, intrinsic pathway, and granzyme B pathway).
  1,227 88 -
REVIEW ARTICLES
Prophylactic role of some plants and phytochemicals against radio-genotoxicity in human lymphocytes
Mohsen Cheki, Ehsan Mihandoost, Alireza Shirazi, Aziz Mahmoudzadeh
October-December 2016, 12(4):1234-1242
DOI:10.4103/0973-1482.172131  PMID:28169233
Genotoxicity in lymphocytes of cancer patients undergoing radiotherapy can lead to lymphocytopenia. Lymphocytopenia induced by radiotherapy is one of the most unfavorable prognostic biological markers in cancer patients, since it has been accepted to be associated with poor prognosis in terms of both survival time and response to cancer therapy. Therefore, reduction in lymphocytopenia may increase treatment efficiency. Research endeavors with synthetic radioprotectors in the past have met with little success primarily due to toxicity-related problems. These disadvantages have led to interest on the use of some plants and phytochemicals as radioprotector. The aim of this paper is to review protective role of some plants and phytochemicals against genotoxicity-induced by ionizing radiation in human blood lymphocytes. Therefore, current review may help the future researches to decrease lymphocytopenia in radiotherapeutic clinical trials.
  1,153 135 -
ORIGINAL ARTICLES
Efficacy of compound Kushen injection plus radiotherapy on nonsmall-cell lungcancer: A systematic review and meta-analysis
Shanshan Wang, Xiaobo Lian, Miaomiao Sun, Lei Luo, Lizhong Guo
October-December 2016, 12(4):1298-1306
DOI:10.4103/0973-1482.199538  PMID:28169243
Objective: To evaluate the benefits of compound Kushen injection (CKI) combined with radiotherapy for nonsmall cell lung cancer. Materials and Methods: We searched nine electronic databases and six gray literature databases comprehensively until June 2015. Two reviewers independently selected and assessed the included trials according to the inclusion and exclusion criteria. The risk of bias tool from the Cochrane Handbook version 5.1.0, the Review Manager 5.3 software was employed for data analysis. Funnel plot and Egger's test were applied to evaluate the publication bias. Results: Thirteen studies including 1558 participants met the inclusion criteria, most of which were low quality. Compared with radiotherapy alone, CKI plus the same radiotherapy significantly improved the effective rate (odds ratio [OR] =1.92, 95% confidence interval [95% CI]: [1.42, 2.60] P < 0.0001) and quality of life (OR = 4.61, 95% CI: [3.28, 6.48], P < 0.00001). There was a significant decrement in the incidences of acute radiation pneumonia (OR = 0.48, 95% CI: [0.37, 0.61], P < 0.00001), radiation pneumonia 3 months after radiotherapy (OR = 0.29, 95% CI: [0.20, 0.41], P < 0.00001), radiation pneumonia 6 months after radiotherapy (OR = 0.24, 95% CI: [0.08, 0.69], P < 0.009), radiation esophagitis (OR = 0.29, 95% CI: [0.19, 0.45], P < 0.00001), and bone marrow suppression (OR = 0.35, 95% CI: [0.24, 0.51], P < 0.00001). Conclusion: CKI combined with radiotherapy significantly improved the clinical effect and reduced the incidence of adverse events. Use of the CONSORT statement for randomized controlled trials is recommended for rigorous reporting.
  1,187 71 -
Prediction of heterogeneity in breast cancer immunophenotype at ductal carcinoma in situ stage?
Manish Rohilla, Amanjit Bal, Gurpreet Singh, Kusum Joshi
October-December 2016, 12(4):1249-1256
DOI:10.4103/0973-1482.199541  PMID:28169235
Introduction: Ductal carcinoma in situ (DCIS) is considered a heterogeneous lesion at the molecular level. However, there is a paucity of literature about the existence of molecular subtypes in DCIS which can predict their biological behavior at the preinvasive stage. Materials and Methods: Precise prevalence of molecular subtypes of pure DCIS and DCIS component of infiltrating duct carcinoma (IDC) was evaluated using immunohistochemistry and correlated with known prognostic factors. Results: DCIS cases were classified as luminal A (46.6% in each group), luminal B (pure DCIS 20% and DCIS component of IDC 13.3%), HER2 overexpressing, basal and nonbasal (pure DCIS 3.3% and 26.6% and DCIS component of IDC 3.3% and 33.3%, respectively), and triple negative, nonbasal (pure DCIS and DCIS component of IDC 3.3% each). The molecular phenotype of DCIS correlated well with that of the coexisting IDC. Conclusions: This study demonstrated molecular heterogeneity in DCIS; however, similar molecular phenotypes were seen in the coexisting IDC suggesting that DCIS is a precursor lesion and can predict phenotype of the invasive component. This also suggests that the invasiveness of DCIS is not dependent solely on the molecular character of the tumor epithelial cells, but factors such as tumor microenvironment may play a role.
  1,153 91 -
The clinical and pathological features affecting the time of relapse in patients with early stage colorectal cancer
Doğan Yazilitas, Nuriye Özdemir, Ozan Yazıcı, Cemil Hocazade, Nebi Serkan Demirci, Nurullah Zengin
October-December 2016, 12(4):1257-1260
DOI:10.4103/0973-1482.199527  PMID:28169236
Background: The relapses of colorectal cancer (CRC) frequently occur in 2 years period after the time of diagnosis. However, a considerable proportion of patients relapse in the late period. Aim: The aim of the present study is to define the factors predicting the early and late relapses of patients with early stage CRC. Materials and Methods: A total of 250 patients with CRC, who relapsed after completion of primary therapy between 2005 and 2014, were enrolled in the study. According to the time of relapse, patients were divided into two groups as follows: Early relapse (Group 1: Within first 24 months) and late relapse (Group 2: Later than 24 months). Clinicopathological features and survival rates of the two groups were compared. Results: Of 250 patients, 151 (60.4%) (Group 1) were relapsed within the first 24 months after completion of the primary therapy and 105 (39.6%) were relapsed later than 24 months. The patients with T1–T2 and Grade I tumors were relapsed in late period (P < 0.05). The rates of administered systemic chemotherapy and targeted therapies after relapse were similar in both groups. The median overall survival rates in patients relapsed within the first 24 months and after 24 months were 18 months and 21 months, respectively (P = 0.05). Conclusions: In patients with CRC, the time duration of relapse after completion of the operation and adjuvant chemotherapy was a prognostic factor. Grade I and superficial tumors (T1–T2) are the predictors of late relapses (after >24 months). The patients relapsed within the first 24 months after primary therapy had poor prognosis compared to those who relapsed in late period.
  1,142 69 -
E-JCRT CORRESPONDENCE
21 cases reports on haemangioma of spleen
Yuan Huang, Guangchuan Mu, Xingan Qin, Jinling Lin, Shaosen Li, Yanjun Zeng
October-December 2016, 12(4):1323-1323
DOI:10.4103/0973-1482.199575  PMID:28169248
The growing activity of hemangioma of spleen keeps unknown. To search theoretical basis for whether to take the operation, this study analyzed clinical data of 21 hemangioma patients, and 16 surgical specimens were analyzed immunohistochemistry of Ki-67, Bcl-2 and vascular endothelial growth factor (VEGF). Both 14 cases of cavernous hemangioma were positive for VEGF, and negative in capillary hemangioma, there was statistical significant difference between two types of hemangioma (P < 0.05). The most tumors had a low expression of Ki-67 with a mean ± standard deviation (SD) of 6.62 ± 6.24%, whereas the mean ± SD of Bcl-2 labeling index was 36.06 ± 19.05%. According to the statistical results, the expression of Ki-67 and Bcl-2 did not correlate with age, gender, tumor size, amount of tumor and angiomatous types. Hemangioma of spleen was one benign tumor with a tendency of slow growth. Therefore, operation should be strictly selected, we recommend observation of patients with small, asymptomatic splenic lesions, which meet the radiologic criteria for hemangiomas.
  947 134 -
ORIGINAL ARTICLES
Modified mismatch polymerase chain reaction-restriction fragment length polymorphism detected mutations in codon 12 and 13 of exon 2 of K-ras gene in colorectal cancer patients and its association with liver metastases: Data from a South Asian country
Fathima Dhilhani Mohamed Faleel, M. I. M. De Zoysa, M. D. S. Lokuhetti, Y. I. N. S. Gunawardena, Vishvanath Naduviladath Chandrasekharan, Ranil Samantha Dassanayake
October-December 2016, 12(4):1272-1277
DOI:10.4103/0973-1482.187294  PMID:28169239
Aim: Mutations in K-ras codon 12 and 13 of exon 2 are known to affect prognosis and impart resistance to anti-epidermal growth factor monoclonal antibody therapy in colorectal carcinoma (CRC). Our aim was to investigate the utility value of modified mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to detect mutation in K-ras codons of CRC patients and to relate the mutational status to liver metastasis. Methodology: Mismatch PCR-RFLP was developed to detect K-ras mutations in DNA isolated from paraffinized tumor tissue of thirty CRC patients. All patients had 5 year follow-up data to detect liver metastasis. Cross-tabulations were generated between K-ras mutations and the metastatic status. The Chi-square test was used to indicate statistical significance of the association. Results: Of the 30 CRC patients investigated, K-ras mutations of codons 12 and/or 13 of exon 2 were detected in 14 (46.6%). Meanwhile, 13 patients (43.3%) were observed to have developed liver metastases. There was a significant association between the presence of the K-ras mutation in codon 12 and the occurrence of liver metastasis (χ2 = 4.693, P = 0.030) on the contrary to the mutation in codon 13 to which such occurrence of liver metastases was not seen (χ2 = 1.884, P = 0.169). Conclusion: Codon 12 of exon 2 of K--ras gene detected by modified mismatch PCR-RFLP assay is significantly associated with liver metastasis in CRC patients during the first 5 years after surgery. Thus, modified mismatch PCR-RFLP protocol is a suitable method in this setting to detect K-ras gene mutations predicting liver metastasis in CRC patients.
  1,005 72 -
Expression of metallothionein in dimethylhydrazine-induced colonic precancerous and cancerous model in rat
Pamela Christudoss, Geeta Chacko, Ratnasamy Selvakumar, Jude Joseph Fleming, Srinivasan Pugazhendhi, George Mathew
October-December 2016, 12(4):1307-1312
DOI:10.4103/0973-1482.179107  PMID:28169244
Aim: Metallothionein (MT) is a small protein with a high affinity for divalent heavy metals and has a function in zinc homeostasis. The purpose of this study was to assess the MT mRNA gene expression as well as the MT protein content by immunohistochemistry and radioimmunoassay (RIA) in 1,2-dimethylhydrazine (DMH)-induced precancerous and cancerous colonic tissue in rats. Materials and Methods: Six-week-old rats were given subcutaneous injections of DMH twice a week for 3 months and sacrificed at 4 months (precancerous model) and 6 months (cancerous model). We determined MT mRNA expression by reverse transcription polymerase chain reaction and MT protein content by both immunohistochemical expression and cadmium-109 RIA. Results: MT mRNA expression in the large intestine showed statistically significant decrease in the precancerous (P < 0.01) and the cancerous (P < 0.001) model as compared with controls. Immunohistochemical expression of MT showed statistically significant decrease (P < 0.05) in the colonic cancerous tissue. MT content in the large intestine showed statistically significant decrease in precancerous (P < 0.005) and cancerous (P < 0.001) model as compared with controls. Conclusion: This study suggests that a decrease in the colonic MT mRNA expression, MT protein expression, and content in DMH-induced colonic cancer model is associated with the development of preneoplastic lesions and further progression to carcinoma in the colon results in a greater reduction in the levels of each of these parameters.
  891 68 -
(Z)-3,4,3',5'-tetramethoxystilbene, a natural product, induces apoptosis and reduces viability of paclitaxel-and cisplatin-resistant osteosarcoma cells
Huiqing Xu
October-December 2016, 12(4):1261-1265
DOI:10.4103/0973-1482.158035  PMID:28169237
Aim of Study: Osteosarcoma is a common bone tumor and the development of drug resistance in therapy of osteosarcoma is a general rule. The natural compounds isolated from medicinal plants represent a valuable resource for anticancer therapeutics. (Z)-3,4,3', '-tetramethoxystilbene is one of them. In this work, we investigated the potential anti-cancer activities of (Z)-3,4,3' ,'5-tetramethoxystilbene in paclitaxel- and cisplatin-resistant osteosarcoma cells. Materials and Methods: ATP assay was used to examine cell viability. Cell nuclei staining assays with Hoechst or propidium iodide (PI) were used to evaluate cell apoptosis. Xenograft tumor model was used to evaluate the in vivo anti-cancer activities of (Z )-3,4,3',5'-tetramethoxystilbene. TUNEL staining assay was used to evaluate the apoptosis of tumor cells. Results: We found that (Z)-3,4,3',5'-tetramethoxystilbene could effectively reduce viability of both paclitaxel-and cisplatin-resistant osteosarcoma cells. Moreover, (Z)-3,4,3',5'-tetramethoxystilbene induced dramatic apoptosis in resistant cells. Importantly, (Z)-3,4,3',5'-tetramethoxystilbene significantly suppressed in vivo tumor growth of cisplatin-resistant osteosarcoma. Conclusion: This is the first report on anti-cancer activity of (Z)-3,4,3','5- tetramethoxystilbene in resistant osteosarcoma cells. Our studies suggest that (Z)-3,4,3',5'-tetramethoxystilbene is a promising therapeutic drug for overcoming drug resistance in osteosarcoma.
  862 67 -
EDITORIAL
One last time
Nagraj Huilgol
October-December 2016, 12(4):1215-1215
DOI:10.4103/0973-1482.199543  PMID:28169229
  833 94 -
ORIGINAL ARTICLES
Increased expression of high-mobility group A2: A novel independent indicator of poor prognosis in patients with esophageal squamous cell carcinoma
Rongna Wei, Zhiqun Shang, Jing Leng, Lihong Cui
October-December 2016, 12(4):1291-1297
DOI:10.4103/0973-1482.180616  PMID:28169242
Purpose: Although high-mobility group A2 (HMGA2) protein has been reported to participate in cancer progression and metastasis, its clinical relationship with tumor invasion, lymph node metastasis, and prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to analyze the clinical and prognostic significance of HMGA2 in ESCC patients after curative resection. Materials and Methods: The expression of HMGA2 protein was evaluated by using immunohistochemistry in a tissue microarray (TMA) containing ESCC lesions and adjacent normal esophageal epithelial tissues from 96 patients who had undergone curative resection. TMA was constructed by Shanghai Biochip Co. Ltd., Shanghai, China. The relationship between HMGA2 expression and clinicopathological parameters and prognosis was further analyzed. Results: HMGA2 expression was significantly higher in ESCC tissues compared with that of the adjacent noncancerous tissues (P < 0.001). High expression of HMGA2 was significantly related to tumor size, lymph node metastasis, and advanced tumor-node-metastasis stage (P < 0.05). Patients with low expression of HMGA2 had a better prognosis than those with high expression (χ2 = 5.069, P = 0.024). Univariate analysis showed that age (P = 0.041), depth of tumor invasion (P = 0.031), lymph node status (P = 0.001), and HMGA2 expression (P = 0.024) were correlated with prognosis. Multivariate analysis showed that HMGA2 expression (hazard ratio [HR]: 0.539; 95% confidence interval [95% CI]: 0.302–0.963, P = 0.037) and lymph node metastasis (HR: 0.504; 95% CI: 0.310–0.820, P = 0.006) were independent prognostic factors for overall survival. Conclusions: High HMGA2 expression was related to lymph node metastasis and poor prognosis in ESCC. Our results indicated that HMGA2 could act as a potential biomarker for prognosis evaluation of ESCC patients.
  851 45 -
ORIGINAL ARTICLE
Evaluation of hypoxia inducible factor-1 alpha gene expression in colorectal cancer stages of Iranian patients
Reyhaneh Nassiri Mansour, Seyed Ehsan Enderami, Abdolreza Ardeshirylajimi, Koorosh Fooladsaz, Mojtaba Fathi, Shahla Moahammad Ganji
October-December 2016, 12(4):1313-1317
DOI:10.4103/0973-1482.199542  PMID:28169245
Aim of Study: Colorectal cancer (CRC) is the fourth most prevalent cancer globally. Several factors have roles in cancer establishment. One of the most important factors is hypoxia that induces hypoxia inducible factor-1 (HIF-1). The HIF-1 alpha overexpressed in hypoxia conditions and plays a pivotal role in carcinogenesis features. In this study, we aimed to examine the efficiency of HIF-1 alpha gene expression at mRNA and protein's level for CRC diagnosing and staging. Materials and Methods: In this study, the cases included into 75 cancer specimens in different stages (Group 2 = Stage 1, Group 3 = Stage 2, and Group 4 = Stage 3, 4) and ten normal specimens as control (Group 1). Real-time reverse transcription-polymerase chain reaction and immunohistochemistry (IHC) were performed for measuring gene expression at RNA and protein's level, respectively. The raw data were analyzed in the SPSS20 software. Results: HIF-1 alpha gene expression rate (2ΔΔCT) and ΔCT values were significantly higher increased in Group 4 in compare to control (P < 0.001). Other cancer groups (2 and 3) had greater ΔCT values than control, but it was not statistically significant. Moreover, the rate of HIF-1 alpha gene expression (2ΔΔCT) was increased with cancer stages. According to the IHC results, there was a positive relationship between CRC stages and HIF-1 alpha protein expression (P < 0.05). Conclusions: HIF-1 alpha gene expression increased in earlier up to metastasis stages of CRC, but the assessment of HIF-1 alpha gene expression has not important role in the diagnosis of cancer in early stages and classification of carcinoma because the increasing of HIF-1 alpha gene expression is not significant in early cancer stages.
  593 152 -
CORRESPONDENCE
The diagnosis of mesenteric fibromatosis: A 90-month five patients case report
Peixin Li, Zhongtao Zhang, Shengqi Qin, Jianshe Li
October-December 2016, 12(4):1318-1320
DOI:10.4103/0973-1482.199539  PMID:28169246
Mesenteric fibromatosis (MF) is a rare tumor (2–4 cases per 1 million people annually) with few presented features. In this case study, we reported five MF patients, one of whom suffered a recurrence. Patients received renogram, colonoscopy, cystoscopy, and gastrointestinal examinations. Histology and immunohistochemistry evaluations were performed after the surgical resection. Hormone levels were measured before and after the surgery. It was found that clinical imaging readily confirmed an abnormal mass but was unable to distinguish MF from other tumors. Histology and immunohistochemistry were definitive diagnoses because the tissue was vimentin ± β–catenin ± CD117/CD34. Furthermore, the patient who suffered a recurrence showed an elevated estrogen level. A 6-month postoperative administration of letrozole drove the estrogen down to normal level. Our study showed that vimentin, β–catenin, CD117, and CD34 were the markers for MF whereas medical imaging, and estrogen level could be used for the complimentary purpose.
  673 62 -
BOOK REVIEW
Science set free: 10 paths to new discovery
CR Sridhar
October-December 2016, 12(4):1321-1322
  265 27 -