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Table of Contents
January-February 2017
Volume 6 | Issue 1
Page Nos. 1-122
Online since Thursday, June 29, 2017
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REVIEW ARTICLE
Role of oxidative stress in liver cancer
p. 1
Hossein Forouzandeh, Heibatullah Kalantari, Najmaldin Saki, Zahra Foruozandeh, Ehsan Arefian, Abbas Farahani, Ghasem Hassani, Mohammad Rafi Bazrafshan, Shima Rasouli
DOI
:10.4103/ccij.ccij_176_16
The present article provides an overview of the role of oxidative stress in the development and progression of liver cancer (LC). Oxidative stress ensues when the balance between the production of reactive oxygen species (ROS) and reactive nitrogen species overrides the antioxidant defense of the target cell and body fails in detoxifying their harmful effects. Therefore, the interaction of these reactive species with critical cellular macromolecules may cause oxidative damage. Moreover, ROS may interact with cellular components including proteins, lipids, and DNAs, which results in altered target cell function. The accumulation of oxidative damage products has been implicated in both acute and chronic cell injury suggesting a possible role in the pathogenesis of Parkinson's disease, Alzheimer's disease, atherosclerosis, heart failure, myocardial infarction, and cancers. Alcoholism, viral agents, obesity, and smoking increase the occurrence of oxidative stress and consequently the risk of LC.
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ORIGINAL ARTICLES
Prostate cancer detection in patients with total serum prostate-specific antigen levels of 4–10 ng/mL: Diagnostic efficacy of MicroRNA-141
p. 10
Abdulkadir Cat, Tülay Köken, Mustafa Karalar
DOI
:10.4103/ccij.ccij_16_17
Objective:
The purpose of this small pilot study was to evaluate the utility of microRNA-141 (
miR-141
) as a biomarker for detecting prostate cancer (PCa) in patients with total serum prostate-specific antigen (PSA) levels of 4–10 ng/mL, which is referred to as the “gray zone.”
Materials and Methods:
Eleven PCa patients, 23 benign prostatic hyperplasia (BPH) patients with PSA levels of 4–10 ng/mL, and 16 healthy controls were enrolled in this study. Total RNA was extracted from serum samples, and the level of
miR-141
was analyzed by quantitative reverse transcription polymerase chain reaction.
Results:
The circulating
miR-141
level was significantly higher in PCa patients than in BPH patients and healthy controls (fold change [mean ± standard deviation], 0.528 ± 0.083 for PCa, 0.297 ± 0.038 for BPH, and 0.262 ± 0.025 for controls;
P
< 0.05). Receiver operating characteristic curve revealed that the serum
miR-141
yielded an area under the curve of 0.751, with 72% sensitivity and 92% specificity in discriminating patients with PCa from BPH patients with total serum PSA levels in the gray zone.
Conclusion:
The present results indicate that
miR-141
expression is significantly increased in the peripheral blood of patients with PCa compared with BPH patients and healthy individuals. We think that
miR-141
may guide clinicians during the decision phase of patients with PCa and BPH in the PSA gray zone.
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Anatomic distribution and histologic subtypes of primary gastrointestinal lymphomas: A retrospective analysis of 152 cases
p. 15
Renu Sukumaran, Rekha A Nair, Priya Mary Jacob, Jayasudha A Vasudevan, Geetha Narayanan, T Priya Kumary
DOI
:10.4103/ccij.ccij_174_16
Background:
Gastrointestinal (GI) lymphomas are a heterogeneous group of neoplasms. Studies have demonstrated a wide variation in the sites of involvement and histologic subtypes, which are independent prognostic factors. Hence, it is important to study the frequency and distribution pattern of GI lymphoma in a particular region. Aim: The aim of this study was to study all cases of primary GI lymphomas presented to our center for 5 years with reference to the pattern of distribution and histologic subtypes and compare our data with the literature.
Materials and Methods:
In this retrospective study, all cases of primary GI lymphomas over a period of 5 years from 2010 to 2014 were analyzed.
Results:
There were 152 cases of primary GI lymphomas. Age ranged from 3 years to 83 years. There were 133 adult patients and 19 pediatric patients. Most common site of involvement was small intestine followed by stomach, large intestine, and esophagus. Most common histologic subtype was diffuse large B-cell lymphoma (DLBCL), followed by Burkitt lymphoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, follicular lymphoma, mantle cell lymphoma, B-cell lymphoma unclassifiable with features intermediate between DLBCL and Burkitt lymphoma, and plasmablastic lymphoma. There were five cases of T-cell non-Hodgkin lymphoma which included adult T-cell leukemia/lymphoma, anaplastic large-cell lymphoma, enteropathy-associated T-cell lymphoma, and T-lymphoblastic lymphoma. One case of Hodgkin lymphoma with predominant involvement of the large intestine and without any peripheral node involvement was also encountered.
Conclusion:
In our series, the most common site of involvement was the small intestine. This is in contrast to majority of studies where the most common site is the stomach. Similar to the other studies, DLBCL was the most common histologic subtype. Compared to other studies, there were more number of Burkitt lymphoma and lesser number of MALT lymphoma in our series.
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A study of head and neck cancer patients with special reference to tobacco use and educational level
p. 21
Rajjyoti Das, Amal Chandra Kataki, Jagannath Dev Sharma, Nizara Baishya, Manoj Kalita, Manigreeva Krishnatreya
DOI
:10.4103/ccij.ccij_24_17
Background:
In India, head and neck cancers (HNCs) are common and constitute 20%–30% of all cancers. The most common risk factors are consumption of tobacco and alcohol. Betel nut chewing with or without tobacco is a major risk factor for HNC in India, especially in the Northeast India.
Materials and Methods:
This was a hospital-based retrospective study to measure the descriptive scenario of HNC cases along with their demographic and risk factor profile. The patients diagnosed from June 01, 2014, to December 31, 2014, were included in the study. The data of patients were analyzed for age, gender, subsites, stage at diagnosis, pattern and prevalence of tobacco usage, and different education level of patients. Chi-square test was performed to assess the association of gender and tobacco habits.
Results:
One thousand four hundred and twenty-eight patients were included in the study, M: F was 4:1, hypopharynx in males (36.2%) and mouth in females (39.8%) were leading HNC sites, and majority (83.8%) presented in locally advanced stages. Majority of patients (34.1%) and tobacco users (34.7%) were illiterates, and 82.9% of all HNC patients were tobacco users. Males with cancers of the tongue, hypopharynx, and larynx (
P
< 0.05) were significantly at an increased risk of developing HNC with tobacco consumption.
Conclusion:
Our findings suggest that improvement in the education level may lead to decline in the use of tobacco and thereby reduction in the burden of HNC patients.
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p53 expression in colorectal carcinomas and its correlation with clinicopathological parameters
p. 26
Kavita Mardi, Manika Sharma, Meena Bhardwaj, Manju Rao
DOI
:10.4103/ccij.ccij_5_17
Background:
p53 over expression is based on the fact that the mutant form of p53 protein having prolonged half-life can accumulate and be over expressed in nuclei which can easily detected by immunohistochemistry.
Objective:
To estimate the frequency of p53 protein overexpression in colorectal carcinoma and its correlation with some clinicopathologic parameters.
Methods:
The overexpression of p53 protein was studied in sixty paraffin-preserved colorectal carcinoma samples using a monoclonal antibody (clone DO-7). The number of cells stained were scored semiquantitatively as (score 0): <5% positive cells, (score 1+): 5 – 25% positive cells,(score 2++): 25 – 75% positive cells, and (score 3+++): >75% positive cells..The correlation between p53 protein over expression and clinicopathological parameters were evaluated using Chi-square analysis.
Results:
p53 staining was positive in 42 of 60 specimens. Out of these , 10 were weekly (score1+), 16 moderately (score 2++), and 16 intensely(score 3+++) positive for P53 protein overexpression. There was statistically significant correlation between p53 staining and age(< 40 years vs >= 40 years; P- 0.006). Statistically significant correlation was also found between p53 staining and pathological type( mucinous vs non mucinous; p- 0.007) There were no significant correlations between p53 staining and gender (P =0.86 ), site of tumor (right colon vs. left colon and rectum; P=0.69) and stage of the disease (P =0.34 ).
Conclusion:
As p53 protein overexpression is seen in relatively high percentage of patients of colorectal carcinoma., it seems that p53 mutation plays an important role colorectal carcinogenesis. There was significant association between p53 protein expression and some common clinicopathologic variables such as age and pathologic type ( mucinous/nonmucinous), whereas no significant association was found between p53 expression and other parameters like gender, site of tumor, tumor grade and stage of the disease.
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Precancerous breast lesions in benign breast lesions: Review of 430 benign breast lesions
p. 30
Shirish S Chandanwale, Supreet Kaur, Rahul Nair, Jay Y Sheth, Sanjyot Nikam, Jehan Nizam Ansari, Manpreet Kaur, Ashily Koshy
DOI
:10.4103/ccij.ccij_7_17
Background:
Unanimously recognized precancerous breast lesions are atypical ductal hyperplasia (ADH), atypical lobular hyperplasia, flat epithelial atypia, lobular carcinoma
in situ
, papillary lesions, and proliferative radial scar. The increased risk of developing carcinoma associated with these lesions is found for both ipsi- and contra-lateral breasts. These precancerous lesions are also found in benign breast lesions.
Aim:
The aim of this study is to study histomorphological features of precancerous breast lesions and to find the prevalence of these lesions in various benign breast lesions in different age groups.
Materials and Methods:
We evaluated histomorphology of 430 benign breast lesions for the presence of precancerous breast lesions. The frequency of precancerous lesions was correlated with type of benign breast lesions and different age groups.
Results:
In thirty cases of benign breast lesions, precancerous lesions were found. Maximum cases were of lobular neoplasia (LN) (
n
= 12) followed by papilloma (
n
= 9). Majority of the lesions were found between 31 and 40 years (
n
= 16). Maximum cases of LN (
n
= 6) and ADH and peripheral papilloma each (
n
= 4) were seen in the age group of 31–40 years. Maximum precancerous lesions were seen in fibrocystic change (
n
= 21), followed by sclerosing adenosis (
n
= 5), and fibroadenoma (
n
= 4).
Conclusion:
Prevention is a highly feasible approach to breast cancer control. Benign breast lesions with associated precancerous breast lesions must be separated from pure benign breast lesions. These lesions need future evaluations to assess the risk of carcinoma in ipsilateral as well as contralateral breasts. There is a need for more long-term follow-up studies of precancerous breast lesions in benign breast lesions to assess the risk of developing carcinoma in ipsilateral as well as contralateral breasts.
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Utility of endometrial aspiration cytology for screening postmenopausal women for endometrial malignancies
p. 35
Kavita Mardi, Manju Rao, Meena Bhardwaj, Manika Sharma
DOI
:10.4103/ccij.ccij_151_16
Objective:
Endometrial aspiration cytology (EAC) is an acceptable and valuable diagnostic procedure for screening the endometrial status. Objective of this study is to know the utility of this procedure as a screening procedure for detection of endometrial malignancies in postmenopausal women with abnormal uterine bleeding (AUB).
Methods:
Endometrial aspiration obtained using 5F infant feeding tube attached to 20cc disposable syringe. Endometrial aspiration material was smeared directly on to three clean glass slides.One smear was wet fixed for papanicolau staining and the remaining slides were air dried for Giemsa stain. Smears were reviewed for cytomorphological findings and were correlated with the histopathological findings.
Results:
100 postmenopausal women presenting with abnormal uterine bleeding were studied. Age of the patients ranged from 45 to 70 years. In our study, the sensitivity and specificity in diagnosing malignancy on aspiration cytology were 90% and 96.25% respectively.
Conclusions:
Endometrial aspiration is an effective, useful and a minimally invasive procedure. With an experienced cytologist, it can be used rou-tinely for the screening of postmenopausal women with AUB for endometrial malignancies, provided all the points of discrepancies are taken care of.
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Evaluation of platelet indices in oral squamous cell carcinoma
p. 40
Vidyavathi Kannar, Veena Raja, Turvekere Narayanrao Suresh
DOI
:10.4103/ccij.ccij_170_16
Context:
Platelet indices are markers of inflammation which are being studied in various cancers; however, data for oral cancers are limited.
Aims:
We aimed to study the platelet indices such as platelet count, mean platelet volume (MPV), plateletcrit, and platelet distribution width (PDW) in oral squamous cell carcinoma (SCC) patients and to compare them with healthy controls.
Settings and Design:
Retrospective cross-sectional study.
Subjects and Methods:
The study included 107 patients with oral SCC and 68 controls who did not meet exclusion criteria. Platelet indices were estimated and compared with controls. The results were statistically evaluated.
Statistical Analysis Used:
Student's
t
-test (two-tailed, independent) was used for statistical analysis. The relationship between measured characteristics of continuous data was determined using Pearson's correlation coefficient.
P
<0.05 was considered statistically significant.
Results:
Platelet count was slightly increased in cases though not statistically significant (
P
> 0.05). MPV was significantly increased in cases than controls (
P
< 0.05). Plateletcrit and PDW were similar in both cases and controls.
Conclusions:
Further studies are needed to assess the utility of platelet indices in oral SCC.
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Glial fibrillary acidic protein, CD34, Ki-67, and p53 immunohistochemistry expression study to estimate the concordance between the morphology and the awarded grades of the brain gliomas
p. 44
Moulay Yassine Belghali, Hanane Rais, Saadia Ba-M'hamed, Fatima Zahra Hazmiri, Noureddine El Khoudri, Anass Fakhri, Anass Belbachir, Hasna Elkhiraoui, Abdelmalek Hakmaoui
DOI
:10.4103/ccij.ccij_148_16
Background:
The 2007 WHO grading system of gliomas recognizes four prognostic grades of the latter. Based exclusively on morphological patterns, this classification remains unsatisfactory with rates of diagnostic conflicts between pathologists ranging from 20% to 50%, particularly between Grades II and III. Misestimating the grade implies impertinent care decisions. We evaluated the concordance between grades and morphological characteristics of our series.
Methods:
Our study is a retrospective covering 3 years and wherein the biopsies of 32 formalin-fixed paraffin-embedded brain gliomas were explored. The histopathological diagnosis had been revised, and all cases were stained by immunohistochemical (IHC) technique with glial fibrillary acidic protein (GFAP), Ki-67, p53, and CD34 tumor markers. Comparisons were made between the grades and the IHC results and between the latter and the morphological characteristics of the studied gliomas. We used Kolmogorov–Smirnov test for normal distribution, Chi-square test of Pearson and Fisher test for qualitative variables, Mann–Whitney U-test, and Kruskal–Wallis test for continuous variables. The significance is retained for
P
< 0.05.
Results:
GFAP is expressed in all of the 32 studied tumors. Our markers are more expressive in high-grade gliomas (GFAP [
P
= 0.149], Ki-67 [
P
= 0.001], p53 [
P
= 0.012], and CD34 [
P
= 0,004]). Labeling index increases with the cellular density (Ki-67 [
P
= 0.001], p53 [
P
= 0.031]) and with the mitotic activity (Ki-67 [
P
= 0.001], p53 [
P
= 0.056]). CD34 is more expressive in the presence of endothelial-capillary proliferation (
P
= 0.02), of palisading necrosis (
P
= 0.015), and of nonpalisading necrosis (
P
= 0.076). Ki-67 is more specific and more sensitive than p53 (
P
< 0.001). The value of ideal expression of Ki-67 proposed for our sample is 8.5% (
P
< 0.001). It allows 93.7% of specificity and 75% of sensibility and separates the low grade (I, II) of the high grade (III, IV).
Conclusion:
The results prove the concordance of the established grades and gliomas morphology of our series.
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Estimation and comparison of serum levels of Copper, Zinc and Cu/Zn ratio as markers of disease activity in oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) patients
p. 51
Shaikh Mohd Yunus, Prakash Gadodia, Ritesh Wadhwani, Namrata N Patil, Vinod Kumar Patil, Vinita Murgod, Abhishek Singh Nayyar
DOI
:10.4103/ccij.ccij_18_17
Context:
Trace elements such as copper (Cu) and zinc (Zn) are involved in vital biochemical reactions, including different redox reactions and free radical formation and in maintaining cellular homeostasis. Several studies have been carried out on Cu, Zn, and iron level in the serum, plasma, and tissue of oral pre-malignant and malignant lesions.
Aim:
The aim of this study was the estimation and comparison of serum levels of Cu, Zn, and Cu/Zn ratio in oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) patients.
Subjects and Methods:
Sera of OSMF (
n
= 30) and OSCC (
n
= 30) patients as also of healthy controls was analyzed for the estimation of Cu and Zn using atomic absorption spectrophotometry.
Statistical Analysis:
Analysis of variance was used to compare the results of patients of OSMF, OSCC patients, and the controls. Independent sample's
t
-test was used to compare the mean values between the two groups. Comparison of mean values between different groups was carried out using Student's
t
-test using appropriate level of significance and degrees of freedom.
Results:
Sera levels of Cu were found to be increased while those of Zn were decreased in OSMF and OSSC patients as compared to the healthy controls.
Conclusion:
It could be concluded that altered sera levels of these trace elements can be helpful in early detection, management, and monitoring the efficacy of treatment in OSMF and OSCC patients.
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Clinical profile and outcomes of granulocytic sarcoma among myeloid malignancies treated in a tertiary care center
p. 56
Rajeshwar Singh, Sundaram Viswanath, Dileep Maleskar
DOI
:10.4103/ccij.ccij_164_16
Introduction:
Granulocytic sarcoma (GS) is a rare tumorous collection of immature myeloid cells in extramedullary sites.
Patients and Methods:
We reviewed all treated patients of myeloid malignancies presenting to a tertiary referral Centre for treatment of Malignant disorders in western part of India. Using the database for patients diagnosed between Jan 2010 and Dec 2015, a study was conducted to detect the incidence, clinical features, and outcomes in patient presenting with GS.
Results:
Our study had 400 patients with myeloid malignancies out of which GS was diagnosed in 07 patients which constituted 1.7% of patients of all myeloid neoplasms. All received standard protocol based treatment. Five patients were in complete remission and one had partial remission after treatment.
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Pentoxifylline increased apoptotic effects of tamoxifen on human breast cancer cells
in vitro
p. 62
Ali Ghanbari, Seyed Sohrab Vahdati, Mozafar Khazaei
DOI
:10.4103/ccij.ccij_165_16
Aims:
Several anticancer drugs are being currently used in the treatment of breast cancer; however, there is a need to develop newer therapeutic regimens that owing to higher cytotoxicity and lower resistance. This study was aimed to investigate the effect of pentoxifylline (PTX) in combination tamoxifen (TAM) on viability and apoptosis of breast cancer cell lines
in vitro
.
Methods:
Two human breast cancer cell lines (MCF-7 and MDA-MB-231) were treated with TAM (2 μM) and different doses of PTX (2, 4, 8, or 16 mM) in combination or alone for 24 or 48 h. Cell viability was evaluated by MTT assay, and effect of these drugs on apoptosis was tested by acridine orange/ethidium bromide staining.
Results:
In 48 h treatment, cell viability of both MCF-7 and MDA-MB-231 cells was reduced in all treated groups (
P
< 0.05). In both cell lines, apoptotic index was significantly increased in combined treatment of 2 μM TAM and 16 mM PTX in comparison with each drug alone (
P
< 0.001).
Conclusion:
PTX induced synergistic effect with TAM on cell growth inhibition of breast cancer cells and could be a candidate drug for breast cancer treatment.
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Investigation of microsatellite instability BAT25 and BAT26 in breast cancer patients by conventional polymerase chain reaction
p. 68
Jabbar Salman Hassan, Basim Mohammed Hanon, Ahmed Hasan Mohammed, Thana Rasheed Abd Al-Rahman
DOI
:10.4103/ccij.ccij_160_16
Context:
Breast cancer is the most common cancer among women worldwide, comprising 23% of the 1.1 million female cancers that newly diagnosed each year.
Aims:
The aim is to investigate the existence of microsatellite instability (MSI) in breast cancer of patients.
Settings and Design:
Fifty female patients with invasive ductal breast carcinoma collected. Inclusion criteria of patients include female patients with diagnostic feature of breast cancer and age range 26–42-year-old untreated with chemotherapy or hormonal therapy.
Subjects and Methods:
DNA had be extracted from frozen tissue samples of breast cancer. This protocol done according to the kit manufacture's manual of QIAamp DNA Mini Kit from Qiagen – USA. All samples tested for MSI by singleplex polymerase chain reactions (PCRs) using two microsatellite markers BAT25 and BAT26. PCR achieved in a final volume of 50 μl and after thermal cycles, gel visualization performed.
Statistical Analysis Used:
The significance of differences in proportions was analyzed using the Fisher's exact test with SPSS version 20 and values of
P
≤ 0.001 considered statistically significant.
Results:
PCR demonstrating MSI in 13 (26%) of the 50 breast cancer sample. Eight (16%) of 50 breast cancer sample were BAT25 positive with a PCR product size of 124 bp, whereas 5 (10%) of 50 breast cancer sample were BAT26 positive with a PCR product size 121 bp.
Conclusions:
The result suggests strong evidence that MSI at the BAT25 and BAT26 and have involved in the pathogenesis of the great majority of breast cancers.
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Efficacy of combined administration of chemoimmunotherapy with bone marrow cells or granulocyte-colony stimulating factor-mobilized stem cells on expansion of myeloid and stem cells
p. 73
Soha Gomaa Ramadan Abdel Salam, Mohamed Labib Salem, Mohamed Nassef, Said Hammad Abdu, Rania El-Adl
DOI
:10.4103/ccij.ccij_4_17
Background:
Integrating immunotherapy and chemotherapy is most likely to be the basis for new optimism in targeting cancer therapies to form local tumor microenvironment and attack tumors early in their development. This regimen has some potential risks such as myelo- and immunosuppression and chemo-resistant tumor cells.
Aim:
The present study aimed to investigate the combination of chemotherapy, immunotherapy, and the prospective of mobilized stem cells for optimization and modulation of the immune system to overcome immunosuppression and kill distant cancer cells.
Materials and Methods:
Ehrlich ascetic carcinoma (EAC) cell line-bearing mice treated with cyclophosphamide (CTX) followed by adoptively transferred with
in vitro
-activated T-cells either harvested from naïve or EAC-bearing host with or without unfractionated bone marrow (BM) cells or granulocyte-colony stimulating factor-mobilized hematopoietic stem cells (HSCs) 1-day post-CTX treatment. All mice were vaccinated with EAC lysate and Hiltonol.
Results:
Cotransfer of activated T-cells obtained from EAC-bearing mice with HSC-progenitors induced the highest antitumor effect through increasing the percentage of apoptosis and decreasing DNA replication in S phase of EAC cells. Besides, marked an increase in the percentage of myeloid cells in spleen and stem cell populations in BM cells. Interestingly, Adoptive T-cell transfer (ACT) derived from EAC-bearing host with or without BM cells induced mobilization of stem cells from BM to circulation increasing their expansion.
Conclusion:
Combination of chemotherapy with ACT plus vaccination may constitute a potent antitumor therapy that provides more efficacious antitumor responses when it is combined with BM cells fostering more effective antitumor immunotherapy strategies.
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Analysis of DNA methyltransferase 3A gene mutations in patients with Philadelphia-negative myeloproliferative neoplasms
p. 81
Neda Ketabchi, Mostafa Paridar, Javad Mohammadi-Asl, Alireza Abooali, Maria Kavianpour, Najmaldin Saki
DOI
:10.4103/ccij.ccij_9_17
Context:
Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) from a group of disorders characterized by dysregulated JAK-STAT functionality, abnormal hematopoiesis, as well as increased production of proliferative cytokines. In addition to JAK2
V617F
mutation, additional gene alterations that are involved in epigenetic mechanisms, particularly
de novo
DNA methyltransferase 3A (DNMT3A), have been described in Ph-negative MPN biology. Aims: The aim of this study is to evaluate the H/C/S/P mutations in codon R882 of DNMT3A gene among patients with Ph-negative MPNs.
Subjects and Methods:
This study was conducted on 64 newly diagnosed patients with PV, ET, and PMF who referred to Shafa Hospital, Ahvaz, Iran. In the beginning, 5 mL whole blood was drawn from each patient, and the DNMT3A R882 codon mutations were investigated following the isolation of peripheral blood mononuclear cells by DNA amplification protocol using polymerase chain reaction and DNA sequencing techniques.
Results:
The R882H G > A mutation, which results in an amino acid substitution at position 882 of DNMT3A gene from arginine (R) to histidine (H), was observed in two patients (3.1%) with JAK2
V617F
positive PV and JAK2
V617F
negative PMFs.
Conclusions:
Based on the results, DNMT3A-R882 mutations occur at a low frequency in patients with Ph-negative MPNs. To the best of our knowledge, this is the first study to specifically estimate the prevalence of DNMT3A mutations among Ph-negative MPN patients living in the Middle East. It is recommended to investigate these mutants as a secondary defect along with common major complications in such patients.
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Sequencing myeloproliferative leukemia exon 10 mutations in iranian patients with breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1-negative myeloproliferative neoplasm
p. 86
Maria Kavianpour, Mohammad Ali Jalali Far, Javad Mohammadi Asl, Ahmad Ahmadzadeh, Tina Vosughi, Neda Ketabchi, Najmaldin Saki
DOI
:10.4103/ccij.ccij_11_17
Context:
Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (
BCR-ABL1)
-negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are distinguished by the dysregulated Janus kinase (JAK)-signal transducer and activator of transcription functionality, abnormal hematopoiesis, and spontaneous proliferation. Moreover, a mutation in
JAK2
V617F
as well as myeloproliferative leukemia
(MPL)
mutations have been reported in these patients, which could be important in the pathogenesis of diseases.
MPL
plays a role in the development of megakaryocytes and platelets as well as self-renewal of hematopoietic stem cells. Aims: The aim of the present study was to investigate the frequency of
MPL
mutations in patients with
BCR-ABL1
-negative MPNs.
Settings and Design:
This study was a cross-sectional study conducted as an analytical, descriptive review.
Subjects and Methods:
This study was performed on 54 newly diagnosed patients with
BCR-ABL1
-negative MPN (PV, ET, and PMF) who referred to Shafa Hospital, Ahvaz, Iran. Five milliliter whole blood was drawn from these patients;
JAK2
V617F
mutation and mutations in exon 10 of
MPL
gene were investigated using polymerase chain reaction and DNA sequencing techniques following the isolation of mononuclear cells from the blood.
Statistical Analysis:
All the data were presented as mean ± standard deviation and were analyzed by SPSS. Results:
JAK2
V617F
mutation was present in 33 patients, among whom there were 6 ET (35.3%), 7 PMF (41.2%), and 20 PV cases (100%).
MPL
W515 L/K
mutation was found in only one case of PMF, which was negative for
JAK2
V617F
mutation. The prevalence of these mutations was 1.8%, and the patient had splenomegaly with lower white blood cell counts and hemoglobin concentration than normal.
Conclusions:
Based on the results,
MPL
mutations rarely occur in patients with MPN. These mutations could be co-expressed with
JAK2
mutations and might be helpful for detecting MPN patients with no
BCR-ABL1
translocation or
JAK2
V617F
mutation.
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Colorectal cancer presenting as ovarian metastasis
p. 92
Loknatha Dasappa, KC Lakshmaiah, Govind Babu, Linu Jacob Abraham, Suresh Babu, Rekha V Kumar, KN Lokesh, LK Rajeev, AH Rudresha, Suparna Ajit Rao, Sunny Garg
DOI
:10.4103/ccij.ccij_14_17
Background:
Metastatic malignant tumors account for up to 7% of ovarian masses. Approximately 3.6% to 7.4% of patients with colon cancer have ovarian metastasis at the time of initial presentation, of which 45% are mistaken for primary ovarian tumors.
Methods:
Tumor registry was analyzed retrospectively for the cases of colorectal cancers diagnosed between 2008 and 2013. SPSS version 19 was used for statistical analysis. The survival curves were generated using the Kaplan–Meier method using log-rank test.
Results:
A total of twenty such patients were identified. Median age was 40 years (22–60 years). Seventeen (85%) patients were below 50 years. Most common symptom was abdominal pain (
n
= 11; 55). Carcinoembryonic antigen was elevated in 17 (85%) patients and CA-125 in 15 (75%) patients. Involvement of ovary was bilateral in almost half of the patients (
n
= 11; 55%). Median overall survival was 8 months. It was significantly higher in six patients with ovary-only metastasis as compared to extraovarian involvement, 24 versus 4 months, respectively (
P
= 0.001). Other factors such as extent of extraovarian metastasis, hepatic and peritoneal involvement, and administration of postoperative therapy did not have a significant survival implication.
Conclusion:
A female patient, especially in the premenopausal age, presenting with a pelvic mass should always be suspected for ovarian metastasis from colon cancer, and necessary evaluation should be carried out. Postoperative chemotherapy (5-fluorouracil-based or capecitabine-based) should be incorporated in suitable patients. However, further larger studies are required in this regard.
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Ki-67 and subtype as prognostic and predictive markers of diffuse large B-Cell lymphoma
p. 97
Govind Babu, KC Lakshmaiah, Loknatha Dasappa, Suresh Babu, Linu Jacob Abraham, CS Premalatha, Clementina Rama Rao, LK Rajeev, AH Rudresha, KN Lokesh, Sunny Garg, Ankit Agarwal
DOI
:10.4103/ccij.ccij_12_17
Introduction:
Since patients with similar International Prognostic Index (IPI) scores have varied outcomes, molecular signatures including Ki-67 overexpression have been studied to prognosticate diffuse large B-cell lymphoma (DLBCL), which have shown varied outcomes.
Objective:
To correlate Ki-67 expression with survival in two biologic subgroups of DLBCL.
Materials and Methods:
One hundred and twelve adults with DLBCL between 2008 and 2012 were identified. Ki-67 overexpression was determined using immunohistochemistry.
Results:
A total of 112 patients of DLBCL were identified and included in the study. The median age was 54 years (18–78 years), with a male/female ratio of 1.8:1. Median survival was greater in patients with low Ki-67 (
n
= 32) as compared to high Ki-67 (
n
= 44) (32 m vs. 21.5 m,
P
= 0.033). In the germinal center B-cell (GCB) subtype, low Ki-67 had a better survival as compared to high Ki-67 (35 m vs. 28 m,
P
= 0.044), whereas in the non-GCB (NGCB) subtype, the results were same but statistically insignificant (26.5 m vs. 18 m,
P
= 0.7). In the high IPI arm, low Ki-67 had a better survival (26.5 m vs. 17 m,
P
= 0.02), whereas in low IPI arm, the results were similar but statistically insignificant (39 m vs. 38 m,
P
= 0.837). Survival analysis was done in each treatment arm (CHOP and R-CHOP) based on Ki-67 expression (high or low) in GCB and NGCB arms. No statistically significant difference was noted in any of the four arms; 27.5 m versus 34 m (
P
= 0.738) in high versus low Ki-67 in CHOP-GCB arm, 15 m versus 22 m (
P
= 0.443) in high versus low Ki-67 in CHOP-NGCB arm, 27 m versus 44 m (
P
= 0.104) in high versus low Ki-67 in R-CHOP-GCB arm, and 31 m versus 35 m (
P
= 0.861) in high versus low Ki-67 in R-CHOP-NGCB arm.
Conclusions:
Ki-67 although an indicator of poor outcome, its use to predict outcomes alone in the absence of study of expression of concomitant markers such as myc/BCL6 would cause a bias in results. Furthermore, its relevance in the rituximab era needs further validation.
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BCL2 and subtype as prognostic and predictive markers of diffuse large B-cell lymphoma
p. 103
KC Lakshmaiah, K Govind Babu, Loknatha Dasappa, Linu Jacob Abraham, MC Suresh Babu, CS Premalatha, Clementina Rama Rao, LK Rajeev, AH Rudresha, KN Lokesh, Suparna Ajit Rao, Sunny Garg
DOI
:10.4103/ccij.ccij_13_17
Introduction:
Since patients with similar International Prognostic Index scores have varied outcomes, molecular signatures, including BCL2 overexpression have been studied to prognosticate diffuse large B-cell lymphoma (DLBCL), which have shown varied outcomes.
Objective:
The aim of this study is to correlate BCL2 protein expression with survival in two biologic subgroups of DLBCL. Materials and Methods: A total of 112 adults with DLBCL between 2008 and 2012 were identified. BCL2 overexpression was determined using immunohistochemistry.
Results:
Median survival was greater in BCL2 negative (
n
= 52) than positive (
n
= 44) (36 vs. 24.5 months;
P
= 0.003). In nongerminal center B-cell type (NGCB), BCL2 negativity had a survival advantage over BCL2 positive (36.5 vs. 17 months;
P
= 0.02), similarly in GCB (36 vs. 33 months;
P
= 0.032). Of 109, 66 received CHOP and 43 R-CHOP. R-CHOP arm had a significant survival advantage over CHOP arm (38 vs. 24 months;
P
< 0.05). In CHOP group, GCB had a survival advantage over NGCB (32 vs. 14 months;
P
< 0.05). In R-CHOP group, no significant difference was seen. BCL2 negativity had a survival advantage in CHOP (31 vs. 20.5 months;
P
< 0.05) as well as R-CHOP group (39 vs. 26.5 months;
P
< 0.05). Analysis was performed in each treatment arm (CHOP and RCHOP) based on BCL2 expression (positive or negative) in GCB and NGCB arms. No statistically significant difference was seen in the four arms.
Conclusions:
BCL2 although an indicator of poor outcome, its use to predict outcomes alone in the absence of study of the expression of concomitant markers, such as myc/BCL6 would cause a bias in results. Furthermore, its relevance in the rituximab era needs further validation.
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CASE REPORTS
Fine-needle aspiration cytology of eccrine porocarcinoma of scalp – Report of a rare case with review of literature
p. 108
Subrata Pal, Jyoti Prakash Phukan, Anuradha Sinha, Mrinal Sikder
DOI
:10.4103/ccij.ccij_169_16
Eccrine porocarcinoma is a rare malignant adnexal tumor of duct of eccrine sweat gland. Cytology of eccrine porocarcinoma has been described in very few literatures. Here, we are presenting a case of fine-needle aspiration cytology (FNAC) of eccrine porocarcinoma of scalp, confirmed subsequently by histology. Accurate preoperative diagnosis of eccrine porocarcinoma by FNAC is difficult but determining the malignant nature of the lesion is crucial for a curative surgery. FNAC can be a convenient, safe, and effective approach to solve difficult diagnostic dilemma.
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An atypical presentation in journal of a rare giant chest wall tumor
p. 111
Mahendra Pratap Singh, Seema Mahant
DOI
:10.4103/2278-0513.209143
Pleomorphic liposarcoma (PLS) is a rare high-grade sarcoma that originates commonly in the extremities and on the retroperitoneum. PLS originating in the chest wall is infrequently reported in literature. One such case in an elderly man who presented with a giant anterior chest wall tumor is reported herein. The computed tomography scan of the chest helped in delineating the mass. The diagnosis was confirmed on histopathology. The tumor was managed with a radical excision with reconstruction. The patient underwent follow-up for 1 year during which no local recurrence or metastasis was found. PLS should be considered in the differential diagnosis of primary chest wall tumor.
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A rare case of adrenal rhabdomyosarcoma
p. 114
Debraj Saha, Jahar Majumder, Santu Chejara, Arghya Basu, Soumen Pramanik, Soumyadip Das
DOI
:10.4103/2278-0513.209146
Rhabdomyosarcoma (RMS) of the adrenal gland is a very rare entity in medical literature. Very few case reports are available in the journals. In our case report, we have shared our clinical experience of coming across such a scenario where a 43-year-old woman presented with left-sided adrenal mass, later on proved to be pleomorphic RMS. To the best of our knowledge, this is the second case of pleomorphic RMS of the adrenal gland in an adult diagnosed by light microscopy and immunohistochemical stains.
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Neoadjuvant chemotherapy in locally advanced cancers of oral cavity
p. 116
Ashok Kumar Das, Kaberi Kakati, Nizara Baishya, Partha Sarathi Roy, Amal Chandra Kataki
DOI
:10.4103/ccij.ccij_128_16
Oral cancers constitute a major burden of cancer in northeastern part of India. This can be attributed to the increased consumption of tobacco in various forms such as chewing, snuffing, powder or paste and smoking along with betel nut and areca nut. The majority of patients with oral cavity cancer present in an advanced stage which carries a poor prognosis. We present here a case of locally advanced (T4b) oral cavity cancer where 5-fluorouracil (5FU) and methotrexate (MTX) were used as neoadjuvant chemotherapy to attain a surgically resectable stage. The objective of this case report is to show the efficacy and impact of 5FU and MTX as induction chemotherapy in advanced oral cancers.
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Pleuropulmonary blastoma in a 3-year-old girl: A report of a rare case and review of the literature
p. 119
Shokouh Taghipour Zahir, Mohammad Baghi Yazdi, Flora Motevallian
DOI
:10.4103/ccij.ccij_20_17
Pleuropulmonary blastoma (PPB) is a rare, pediatric soft-tissue sarcoma that mainly occurs in the pleural cavity or lungs. Patients with PPB present with nonspecific symptoms mimicking pneumonia or respiratory distress syndrome. Herein, we report a 3-year-old, female case of PPB presenting with fever, cough, chest pain, and progressive shortness of breath. Chest X-ray demonstrated near complete opacification of the right hemithorax with a mild shift of mediastinum to the left, which could be due to large, right-sided pleural effusion. However, any underlying pneumonic consolidation or mass could not be excluded. On ultrasound, small right-sided pleural effusion was confirmed. However, complex cystic mass with fine septation within the pleural cavity was also identified. A recommendation was made to place a chest tube to decrease the compressive effect on the cardiovascular system and contralateral lung and help the patient with his worsening respiratory compromise. Two days after, initial insertion of the chest tube, tissue fragments were draining out from the tube, which was sent for pathologic evaluation. Histopathologic examination revealed a tumoral lesion composed of spindle cells admixed with islands of cartilage and primitive dark cells, which showed a positive reaction to S-100, vimentin, and desmin in immunohistochemical staining. The findings were consistent with a diagnosis of PPB. The patient received neoadjuvant therapy and then underwent surgical resection. The main interesting feature of the case was tissue collection from the chest tube with no need for biopsy or any other invasive procedure to obtain the tissue samples required for histopathologic analysis.
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© Clinical Cancer Investigation Journal | Published by Wolters Kluwer -
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Online since 01 December, 2011