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Pakistan

Cancer Statistics
Population in 2012: 179.9m
People newly diagnosed with cancer (excluding NMSC) / yr: 148,000
Age-standardised rate, incidence per 100,000 people/yr: 111.8
Risk of getting cancer before age 75:11.8%
People dying from cancer /yr: 101,000
Data from IARC GlobalCan (2012)
Pakistan organiations and resources
Latest Research Publications from Pakistan

Pakistan organiations and resources (8 links)


Latest Research Publications from Pakistan

Lin X, Khalid S, Qureshi MZ, et al.
VEGF mediated signaling in oral cancer.
Cell Mol Biol (Noisy-le-grand). 2016; 62(14):64-68 [PubMed] Related Publications
Increasingly it is being realized that oral cancer arises from genetic/epigenetic mutations, dysregulations of spatio-temporally controlled signal transduction cascades and loss of apoptosis. Epidemiological studies have provided a stronger association between tobacco use (chewed and smoked) and oral cancer. Nevertheless, alcohol has also gained attention as a significant risk factor, having a multiplicative synergistic cancer promoting effect with tobacco. Vascular Endothelial Growth Factor (VEGF) mediated signaling has gained limelight because of its instrumental role in endothelial cell proliferation, survival, invasion, migration, chemotaxis of bone marrow (BM)-derived progenitor cells, vasodilation and vascular permeability. In this review we provide most recent updates on involvement of VEGF/VEGFR signaling axis in oral cancer. We partition this multi-component review into different sections and summarize latest advancements related to therapies against VEGF/VEGFR signaling axis and how microRNAs tactfully modulate VEGF and VEGFR in oral cancers. Data obtained through preclinical and clinical studies has revealed that therapeutic benefits associated with VEGF-targeted therapy are complicated in different cancers and involve myriad of mechanisms. A better understanding of VEGF/VEGFR mediated signaling in oral cancers and testing of novel therapeutic agents in preclinical models will prove to be helpful in effective translation of safest drugs from benchtop to the bedside.

Shafi O
Inverse relationship between Alzheimer's disease and cancer, and other factors contributing to Alzheimer's disease: a systematic review.
BMC Neurol. 2016; 16(1):236 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The AD etiology is yet not properly known. Interactions among environmental factors, multiple susceptibility genes and aging, contribute to AD. This study investigates the factors that play role in causing AD and how changes in cellular pathways contribute to AD.
METHODS: PUBMED database, MEDLINE database and Google Scholar were searched with no date restrictions for published articles involving cellular pathways with roles in cancers, cell survival, growth, proliferation, development, aging, and also contributing to Alzheimer's disease. This research explores inverse relationship between AD and cancer, also investigates other factors behind AD using several already published research literature to find the etiology of AD.
RESULTS: Cancer and Alzheimer's disease have inverse relationship in many aspects such as P53, estrogen, neurotrophins and growth factors, growth and proliferation, cAMP, EGFR, Bcl-2, apoptosis pathways, IGF-1, HSV, TDP-43, APOE variants, notch signals and presenilins, NCAM, TNF alpha, PI3K/AKT/MTOR pathway, telomerase, ROS, ACE levels. AD occurs when brain neurons have weakened growth, cell survival responses, maintenance mechanisms, weakened anti-stress responses such as Vimentin, Carbonic anhydrases, HSPs, SAPK. In cancer, these responses are upregulated and maintained. Evolutionarily conserved responses and maintenance mechanisms such as FOXO are impaired in AD. Countermeasures or compensatory mechanisms by AD affected neurons such as Tau, Beta Amyloid, S100, are last attempts for survival which may be protective for certain time, or can speed up AD in Alzheimer's microenvironment via C-ABL activation, GSK3, neuro-inflammation.
CONCLUSIONS: Alzheimer's disease and Cancer have inverse relationship; many factors that are upregulated in any cancer to sustain growth and survival are downregulated in Alzheimer's disease contributing to neuro-degeneration. When aged neurons or genetically susceptible neurons have weakened growth, cell survival and anti-stress responses, age related gene expression changes, altered regulation of cell death and maintenance mechanisms, they contribute to Alzheimer's disease. Countermeasures by AD neurons such as Beta Amyloid Plaques, NFTs, S100, are last attempts for survival and this provides neuroprotection for certain time and ultimately may become pathological and speed up AD. This study may contribute in developing new potential diagnostic tests, interventions and treatments.

Ilahi NE, Anwar S, Noreen M, et al.
Detection of human papillomavirus-16 DNA in archived clinical samples of breast and lung cancer patients from North Pakistan.
J Cancer Res Clin Oncol. 2016; 142(12):2497-2502 [PubMed] Related Publications
PURPOSE: Over the past few decades, human papillomavirus (HPV) has been recorded as a key player in the development of various genital cancers, most notably cervical cancer. It has also been associated with some non-genital cancers. A subset of oropharyngeal cancers are known to be caused by HPV. Its aetiological involvement has been suggested for breast and lung cancer as well. However, reports regarding the HPV DNA detection vary widely from different parts of the world. Due to scarcity of local data in this regard, the current study aimed at retrospective detection of HPV presence in the archival samples of breast and lung cancer patients from north part of the country.
METHODS: A total of 55 formalin-fixed paraffin-embedded tissue sections of invasive ductal carcinoma of breast (n = 46) and lung (n = 9) were collected for this study. Genotyping for HPV16 and 18 was carried out through PCR.
RESULTS: HPV16 DNA was found in both breast and lung carcinoma samples with the prevalence rate of 17 and 11 %, respectively. An interesting association was found between ER/PR (Oestrogen/Progesterone receptor) and HER2/Neu (Human epidermal growth factor receptor-2) positivity with HPV occurrence in breast tumours.
CONCLUSION: Current study shows the presence of HPV16 DNA in archived clinical biopsy sections from breast and lung cancers (17, 11 %), respectively. A positive correlation of HPV16 presence was found with ER/PR and HER2-positive breast cancers. These initial findings warrant further investigation in order to determine HPV prevalence and aetiological role in local cancers, especially in ER/PR/HER2-positive breast cancers on a larger scale.

Shah SA, Aslam Khan MU, Arshad M, et al.
Doxorubicin-loaded photosensitive magnetic liposomes for multi-modal cancer therapy.
Colloids Surf B Biointerfaces. 2016; 148:157-164 [PubMed] Related Publications
Multifunctional magnetic nanosystems have attracted an enormous attention of researchers for their potential applications in cancer diagnostics and therapy. The localized nanotherapies triggered by the external stimuli, like magnetic fields and visible light, are significant in clinical applications. We report a liposomal system that aims to treat cancer by magnetic hyperthermia, photodynamic therapy and chemotherapy simultaneously. The liposomes enclose clinically used photosensitizer m-THPC (Foscan) and anti-cancer drug doxorubicin, in its hydrophobic lipid bilayers, and contains magnetite nanoparticles in hydrophilic core. Three different sizes of magnetic nanoparticles (10, 22 and 30nm) and liposomes (40, 70 and 110nm) were used in this study. Magnetite single domain nanoparticles forming the magnetic core were superparamagnetic but liposomes expressed slight coercivity and hysteresis due to the clustering of nanoparticles in the core. This enhanced the heating efficiency (specific power loss) of the liposomes under an AC field (375kHz, 170Oe). Cell viability and toxicity were studied on HeLa cells using MTT assay and proteomic analysis. Confocal and fluorescence microscopy were used to study the photosensitizer's profile and cells response to combined therapy. It revealed that combined therapy almost completely eliminated the cancer cells as opposed to the separate treatments. Magnetic hyperthermia and photodynamic therapies were almost equally effective whereas chemotherapy showed the least effect.

Bano R, Ismail M, Nadeem A, et al.
Potential Risk Factors for Breast Cancer in Pakistani Women.
Asian Pac J Cancer Prev. 2016; 17(9):4307-4312 [PubMed] Related Publications
BACKGROUND: Breast cancer is the most common female malignancy worldwide and its incidence is on the rise in Pakistan. The aim of this case-control study was to quantify the association of various risk factors with breast cancer risk among Pakistani women.
MATERIALS AND METHODS: A total of 2,246 women were studied, including 1,238 women with histologically confirmed breast cancer patients and age matched control subjects (N=1008) without breast cancer and other chronic diseases. Subjects were interviewed using a specifically designed questionnaire. Unconditional logistic regression was applied. Subsequent disease-specific mortality was also measured.
RESULTS: In this study, majority of the breast cancer patients (69.59%) were in age ranges of 40s and 50s. BMI greater than 25kg/m2 (OR=1.57; 95%CI, 1.26-1.90 and OR=1.60; 95%CI, 1.26-2.03), marital status of unmarried (OR=2.03; 95%CI, 1.69-2.44), lack of breast feeding, smoking (current or ever), lack of physical activity and post-menopausal status were found to have significant positive associations with breast cancer. It was also observed that increased parity reduced the disease risk. A larger number of cases (58.1%) had their right breast affected while 22.8% had other complications as well.
CONCLUSIONS: This exploratory analysis indicated a number of risk factors to be associated with increased risk of breast cancer. It was also observed that mean age at diagnosis is a decade earlier than in western countries. It is hoped that our findings will facilitate establishment of adequate evidence-based awareness and preventive measures for Pakistani women.

Shah NH, Dar FS, Bhatti AB, et al.
Assigning Treatment to HCC Patients for Transplantation: Utility of a New Decision-Making Tool.
Ann Transplant. 2016; 21:668-674 [PubMed] Related Publications
BACKGROUND The Barcelona clinic liver cancer (BCLC) staging system is considered the standard of care for hepatocellular carcinoma (HCC) management. It has various limitations, including lack of second-line treatment options and combination therapy. We prospectively collected data on our HCC patients based on a new decision-making tool (NDT). The objective of this study was to determine the applicability of this tool and compare it with BCLC for treatment allocation, in particular with respect to liver transplantation. MATERIAL AND METHODS We retrospectively reviewed HCC patients who were managed based on an NDT that was developed in 2012. All patients whose treatment decision was based on this tool between 2012 and 2015 were included. Comparison was made with BCLC. Survival was compared for patients who underwent liver transplantation. RESULTS Based on the NDT, 406 (40.6%) patients were eligible for curative treatment versus only 22 (2.2%) patients based on BCLC. A total of 58 (5.8%) patients underwent liver transplant based on the NDT, while only 2 (0.2%) were transplantable based on BCLC. Estimated 3-year survival for transplanted patients based on the NDT was 73%. There were 41 (4.1%) stage C and 15 (1.5%) stage D BCLC patients who received transplant based on the NDT. Estimated 3-year survival for stage A, C, and D BCLC patients who received transplantation was 100%,72%, and 67%, respectively (P=0.6). CONCLUSIONS The NDT correctly identified a group of HCC patients for liver transplantation who would otherwise have received palliative treatment based on the BCLC algorithm.

Jamil U, Akram MU, Khalid S, et al.
Computer Based Melanocytic and Nevus Image Enhancement and Segmentation.
Biomed Res Int. 2016; 2016:2082589 [PubMed] Free Access to Full Article Related Publications
Digital dermoscopy aids dermatologists in monitoring potentially cancerous skin lesions. Melanoma is the 5th common form of skin cancer that is rare but the most dangerous. Melanoma is curable if it is detected at an early stage. Automated segmentation of cancerous lesion from normal skin is the most critical yet tricky part in computerized lesion detection and classification. The effectiveness and accuracy of lesion classification are critically dependent on the quality of lesion segmentation. In this paper, we have proposed a novel approach that can automatically preprocess the image and then segment the lesion. The system filters unwanted artifacts including hairs, gel, bubbles, and specular reflection. A novel approach is presented using the concept of wavelets for detection and inpainting the hairs present in the cancer images. The contrast of lesion with the skin is enhanced using adaptive sigmoidal function that takes care of the localized intensity distribution within a given lesion's images. We then present a segmentation approach to precisely segment the lesion from the background. The proposed approach is tested on the European database of dermoscopic images. Results are compared with the competitors to demonstrate the superiority of the suggested approach.

Yan PF, Yan L, Zhang Z, et al.
Accuracy of conventional MRI for preoperative diagnosis of intracranial tumors: A retrospective cohort study of 762 cases.
Int J Surg. 2016; 36(Pt A):109-117 [PubMed] Related Publications
BACKGROUND: Conventional magnetic resonance imaging (MRI) is considered a valuable tool for preoperative diagnosis of intracranial tumors. We assessed its accuracy in the diagnosis of intracranial tumors in usual clinical practice.
MATERIALS AND METHODS: MRI reports of 762 patients who had undergone conventional brain MRI prior to surgery were retrospectively reviewed. A 4-grade scoring system was devised to establish diagnostic agreement. Each tumor type was compared with the corresponding pathological diagnoses by dichotomization. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for the overall patient population as well as for each tumor type.
RESULTS: 664 cases (87.1%) were tumor-positive, and 98 cases (12.9%) were tumor-negative. The most common tumor types were meningiomas, gliomas, pituitary adenomas and schwannomas. These four types together comprised 74.5% of all cases reviewed. Sensitivity and PPV for the overall population were 72.0-90.7% and 91.9-95.4%, respectively. Diagnostic accuracy differed among tumor types. Meningiomas, pituitary adenomas, schwannomas and cholesteatomas were more likely to be diagnosed correctly (sensitivities were 82.6-96.9%, 86.1-96.7%, 88.9-98.2% and 91.3-100.0%, respectively); while some other types like solitary fibrous tumors (SFTs) seemed difficult to identify. Gliomas tended to be confused with metastases, meningiomas with SFTs, and pituitary adenomas with craniopharyngiomas.
CONCLUSION: The accuracy of conventional MRI for diagnosing intracranial tumors is generally satisfactory but should not be too heavily relied upon, especially for certain tumor types. In cases of discrepancy, neurosurgeons are encouraged to confer with the reporting neuroradiologists to achieve optimal preoperative diagnoses.

Khan M, Mansoor AE, Kadia TM
Future prospects of therapeutic clinical trials in acute myeloid leukemia.
Future Oncol. 2017; 13(6):523-535 [PubMed] Related Publications
Acute myeloid leukemia (AML) is a markedly heterogeneous hematological malignancy that is most commonly seen in elderly adults. The response to current therapies to AML is quite variable, and very few new drugs have been recently approved for use in AML. This review aims to discuss the issues with current trial design for AML therapies, including trial end points, patient enrollment, cost of drug discovery and patient heterogeneity. We also discuss the future directions in AML therapeutics, including intensification of conventional therapy and new drug delivery mechanisms; targeted agents, including epigenetic therapies, cell cycle regulators, hypomethylating agents and chimeric antigen receptor T-cell therapy; and detail of the possible agents that may be incorporated into the treatment of AML in the future.

Saleem Z, Ahmad M, Hashmi FK, et al.
Impairment of liver synthetic function and the production of plasma proteins in primary breast cancer patients on doxorubicincyclophosphamide (AC) protocol.
Pak J Pharm Sci. 2016; 29(5):1555-1563 [PubMed] Related Publications
Doxorubicin and Cyclophosphamide (AC protocol) combination is usually considered as a first line therapy in newly diagnosed breast cancer patients. Thus, a retrospective observational study was conducted to monitor the effect of AC protocol on liver synthetic functions and production of plasma proteins in breast cancer patients, reporting to specialized cancer care hospital of Lahore, Pakistan. A total of 75 patients (n=75) on AC protocol with breast cancer were observed in this study. The patient data including age, gender, body surface area, dosage, disease status and laboratory biochemical values were recorded by reviewing historical treatment records. Pre-treatment values were taken as baseline values for albumin, globulin, blood urea nitrogen (BUN), albumin/globulin (A/G) ratio and total proteins. The baseline values were compared after each cycle of by applying ANOVA using statistical tool SPSS® version 21. The plasma levels of blood urea nitrogen (BUN), total protein and globulin dropped significantly (p<0.05) in patients of all age groups. However, the albumin levels were not significantly changed (p>0.05). The A/G ratio level increased (p<0.05) as a result of reduction in globulin levels. Significant changes in plasma protein levels were observed in the elderly patients (50 to 65 years) than patients between 20 to 50 years of age. AC protocol impairs liver synthetic functions as observed by decreased blood urea nitrogen (BUN) and plasma protein levels.

Ud Din N, Zhang P, Sukov WR, et al.
Spindle Cell Lipomas Arising at Atypical Locations.
Am J Clin Pathol. 2016; 146(4):487-95 [PubMed] Related Publications
OBJECTIVES: Spindle cell lipomas (SCLs) are benign lipomatous neoplasms that classically arise in the posterior neck, upper back, and shoulders of older male patients. We sought to characterize the occurrence of this entity at nonclassic sites.
METHODS: All cases of SCL arising at atypical sites were retrieved from our archives.
RESULTS: Of 439 total cases of SCL, 57 arose at atypical locations in 32 men and 25 women (age range, 27-79 years). The tumor sites included leg (n = 23), buttock/perineum/inguinal (n = 10), forearm (n = 9), finger (n = 9), foot (n = 2), toe (n = 2), hand (n = 1), and flank (n = 1). CD34 was positive staining in all cases tested (52/52), while desmin was negative in most tumors (48/50). Thirty-eight of 38 cases tested exhibited loss of Rb expression. No cases showed CPM/MDM2 amplification (0/48). No local recurrences have been reported (n = 39).
CONCLUSIONS: SCLs may arise in the trunk, lower extremities, and distal upper extremities. While most SCLs arising in classic sites occur in male patients, there is a relatively equal sex distribution in tumors at atypical sites. Pathologists should be aware that SCLs arise at atypical locations to avoid misclassification as other lipomatous neoplasms, including atypical lipomatous tumor.

Sultan S, Irfan SM, Parveen S, Ali S
Clinico-Hematological Findings for Classical Hodgkin's Lymphoma: an Institutional Experience.
Asian Pac J Cancer Prev. 2016; 17(8):4009-11 [PubMed] Related Publications
BACKGROUND: Classical Hodgkin's lymphoma (cHL) is a B-cell lymphoid neoplasm characterized by a distinctive biological behavior with potentially curable disease characteristics. It is an uncommon hematological malignancy which primarily affects younger individuals. The rationale of this study was to determine its clinico-hematological profile along with stage strati cation in Pakistani patients.
MATERIALS AND METHODS: In this descriptive study, adult patients with Hodgkin's lymphoma were enrolled from January 2010 to December 2014.
RESULTS: Sixty two histopathologically con rmed cases of cHL were identified. There were 42 males and 20 females, with a male to female ratio of 2:1. The mean age was 29.7±13.8 years with the median age of 30. B symptoms were present in 72.5% of patients. Histopathologically, the mixed cellularity type constituted 62.9% of cases, followed by nodular sclerosis in 25.8%, lymphocyte predominant in 9.6% and lymphocyte depleted in 1.6%. Stages I and II were present in 43.5% of patients at disease presentation, with 56.4% in stages III and IV.
CONCLUSIONS: Our analysis shows that clinico-pathological features of Hodgkin's lymphoma in Pakistan are comparable to published data. Mixed cellularity is the commonest histological variant and advanced stage at presentation are common findings in our patients.

Idrees F, Fatimi SH, Pervez S
Young man with dyspnoea for 6 months; presenting with subacute tracheal obstruction due to leiomyoma.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Tracheal leiomyoma is a rare benign tumour with less than a 100 cases reported in the literature. We report a case of leiomyoma initially presenting and being treated as asthma until it lead to life-threatening tracheal obstruction, requiring immediate surgical intervention.

Ilahi NE, Hashmi SN, Anwar S, Murad S
Retrospective analysis of HPV 16/18-related disease burden using archival clinical samples.
J Cancer Res Clin Oncol. 2016; 142(11):2367-73 [PubMed] Related Publications
PURPOSE: Estimation of HPV-related disease burden lies at the core of effective disease management. HPV testing is heavily reliant on its retrospective detection in archival clinical cancer samples, especially in parts of the world where HPV screening is not routinely practiced. During the last decade, valuable insights were gained through regional reports based on occasional screening of cervical smears or biopsy sections for the presence of high-risk HPV. HPV 16 and 18 were found to be predominant high-risk HPV subtypes with some regional differences and incidences of co-infections, detected mostly through PCR-based methods. In cases of multiple infections, the presence of viral DNA may not signify its etiologic involvement. The current study, therefore, combines PCR-based detection method with the immunohistochemical (IHC) detection of early viral protein E6 expression, in order to obtain a reliable read out for the disease causing viral subtype, especially in cases of co-infections with oncogenic subtypes other than HPV 16 and 18. Immunohistochemistry (IHC) and PCR-based methods are routinely used laboratory techniques in local hospitals. The concordance between IHC and PCR-based analyses may be useful for determining effective method for the retrospective testing of HPV 16 and 18 disease-related burden.
METHODS: A total of 49 paraffin-embedded cervical cancer biopsy sections representing patients from the northwest region of the country were collected from the tertiary care hospital for this study. Genotyping for HPV 16 and 18 was carried out through PCR. The HPV 16/18 E6 protein expression was evaluated by IHC and was compared with the clinicopathological features of cervical cancer.
RESULTS: Molecular analysis of 33 (67 %), E6-expressing paraffin-embedded cervical cancer biopsy sections revealed the presence of HPV 16 (n = 23; 47 %), HPV 18 (n = 6; 12 %) and co-infection (n = 4; 8 %) in 49 tumors through PCR. Despite the PCR-based detection of viral DNA in 37 cervical cancer samples, IHC analysis of E6 expression revealed the etiological involvement of HPV 16/18 in 33 out of 37 cervical cancer samples. Overall, there was 85 % concordance in the results of the two techniques.
CONCLUSION: IHC analysis provides more conclusive evidence regarding the etiological involvement of the viral subtypes, especially in the presence of multiple infections. About two-thirds (67 %) of cervical cancer samples were found to be caused due to HPV 16/18. Latent occurrence of HPV 16 and 18 is suggested in less than 10 % cervical cancer samples which were found to harbor viral DNA without E6 expression. Furthermore, E6 expression was found to be significantly correlated with the tumor grade.

Hassan A, Riaz S, Zafar W
Fluorine-18 fluorodeoxyglucose avid thyroid incidentalomas on PET/CT scan in cancer patients: how sinister are they?
Nucl Med Commun. 2016; 37(10):1069-73 [PubMed] Related Publications
OBJECTIVE: To evaluate the prevalence of malignancy in incidental thyroidal uptake on PET with fluorine-18 deoxyglucose integrated with computed tomography (F-FDG PET/CT) in Pakistani cancer patients and to assess the role of standardized uptake value (SUV) in deciding which lesions to investigate further.
METHOD: We retrospectively reviewed all patients who underwent F-FDG PET/CT scans over a period of 59 months and further analysed those with visually increased thyroidal uptake. Uptake was classified as focal or diffuse.
RESULTS: Out of 10 012 F-FDG PET/CT scans done for evaluation of known, nonthyroid malignancies, 173 (1.7%) showed incidental thyroid uptake. Of these, 29 were malignant (33%; 24 focal, five diffuse) and 58 were benign (67%; 26 focal, 32 benign) cases. The prevalence of malignancy was significantly higher in cases of focal uptake (P=0.002). After controlling for sex, age, and SUV those with focal uptake were 6.5 times more likely to have malignancy compared with those with diffuse uptake. Odds ratio 6.5; 95% confidence interval 2.0-20.9; P less than 0.01. We found no correlation of SUV with the incidence or type of malignancy.
CONCLUSION: Focal thyroid uptake on F-FDG PET/CT imaging should be sonographically correlated and if indicated with cytological analysis. Although diffuse uptake is usually benign, lymphoma is the leading malignant differential. Nonavid lesions have a low likelihood of malignancy.

Muhammad W, Ullah A, Mahmood K, Matiullah
Assessment of national dosimetry quality audits results for teletherapy machines from 1989 to 2015.
J Appl Clin Med Phys. 2016; 17(2):5984 [PubMed] Related Publications
The purpose of this study was to ensure accuracy in radiation dose delivery, external dosimetry quality audit has an equal importance with routine dosimetry performed at clinics. To do so, dosimetry quality audit was organized by the Secondary Standard Dosimetry Laboratory (SSDL) of Pakistan Institute of Nuclear Science and Technology (PINSTECH) at the national level to investigate and minimize uncertainties involved in the measurement of absorbed dose, and to improve the accuracy of dose measurement at different radiotherapy hospitals. A total of 181 dosimetry quality audits (i.e., 102 of Co-60 and 79 of linear accelerators) for teletherapy units installed at 22 different sites were performed from 1989 to 2015. The percent deviation between users’ calculated/stated dose and evaluated dose (in the result of on-site dosimetry visits) were calculated and the results were analyzed with respect to the limits of ± 2.5% (ICRU "optimal model") ± 3.0% (IAEA on-site dosimetry visits limit) and ± 5.0% (ICRU minimal or "lowest acceptable" model). The results showed that out of 181 total on-site dosimetry visits, 20.44%, 16.02%, and 4.42% were out of acceptable limits of ± 2.5% ± 3.0%, and ± 5.0%, respectively. The importance of a proper ongoing quality assurance program, recommendations of the followed protocols, and properly calibrated thermometers, pressure gauges, and humidity meters at radiotherapy hospitals are essential in maintaining consistency and uniformity of absorbed dose measurements for precision in dose delivery.

Siddiqui EU, Kazi SG, Habib MI, et al.
Pattern of relapse in paediatric acute lymphoblastic leukaemia in a tertiary care unit.
J Pak Med Assoc. 2016; 66(8):961-7 [PubMed] Related Publications
OBJECTIVE: To determine the frequency, site and time to relapse from diagnosis, and to see the relationship of relapse with important prognostic factors.
METHODS: The prospective descriptive observational study was conducted at the National Institute of Child Health, Karachi, June 2005 to May 2007, and comprised newly-diagnosed cases of acute lymphoblastic leukaemia. Bone marrow aspiration was done on reappearance of blast cells in peripheral smear and cerebrospinal fluid. Detailed report was done each time when intra-thecal chemotherapy was given or there were signs and symptoms suggestive of central nervous system relapse. SPSS 12 was used for data analysis.
RESULTS: Of the 60 patients enrolled, 4(6.6%) expired and 1(1.7%) was lost to follow-up. Of the 55(91.6%) who comprised the study sample, 35(58%) were males and 25(42%) females. Mean age of relapse was 6.8±3.27 years. Mean time to relapse from diagnosis was 1.3±0.54 years; 12(20%) patients suffered relapse, and of them 5(14%) were boys. Central nervous system relapse in 8(67%) patients was the most common site, with 3(25%) bone-marrow relapses. Out of 12 patient with relapses, 9(75%) had white blood cell count less than 50,000/cm.
CONCLUSIONS: Relapse in acute lymphoblastic leukaemia was common, although treatment modalities are improving day by day.

Iqbal N, Tariq MU, Shaikh MU, Majid H
Pleural effusion as a manifestation of multiple myeloma.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Multiple myeloma is a clonal B-cell malignancy, characterised by proliferation of plasma cells and secretion of paraproteins. These plasma cells accumulate predominantly in the bone marrow; rarely, they invade other areas, especially the thorax. Myeloma presenting with a pleural effusion is rare and reported in only 6% of patients with myeloma. Such patients generally present late and have a poor prognosis. Here, we describe a patient presenting with a lung mass, renal failure and a massive unilateral pleural effusion due to multiple myeloma who was treated successfully.

Khan N, Afridi HI, Kazi TG, et al.
Correlation of Cadmium and Magnesium in the Blood and Serum Samples of Smokers and Non-Smokers Chronic Leukemia Patients.
Biol Trace Elem Res. 2017; 176(1):81-88 [PubMed] Related Publications
It was studied that cancer-causing processes are related with the disproportions of essential and toxic elements in body tissues and fluid. The purpose of the current study was to evaluate the levels of magnesium (Mg) and cadmium (Cd) in serum and blood samples of smokers and nonsmokers who have chronic myeloid (CML) and lymphocytic (CLL) leukemia, age ranged 31-50 years. For comparative study, age-matched smokers and nonsmoker males were chosen as controls/referents. The levels of elements in patient were analyzed before any treatment by atomic absorption spectrophotometer, after microwave assisted acid digestion. The validation of the method was done by using certified reference materials of serum and blood samples. The resulted data indicated that the adult male smokers and nonsmokers have two- to fourfold higher levels of Cd in the blood and sera samples as compared to the referents (p < 0.01), whereas two- to threefold lower levels of Mg was found in blood and serum samples of both types of leukemia patients as related to referent values. The resulted data indicates significant negative correlation among Mg and Cd in leukemia patients and smoker referents. Further studies are needed to clarify the role of these elements in pathogenesis of chronic leukemia.

Bano R, Zafar W, Khan AI, et al.
Breast Lymphoma Treatment Outcomes in a Pakistani Population: 20 Years of Experience at a Single Center.
Asian Pac J Cancer Prev. 2016; 17(7):3631-5 [PubMed] Related Publications
BACKGROUND: Breast lymphomas constitute a rare disease entity. To date, limited relevant data have been reported. We therefore here present a review of breast lymphoma patients treated at a single center over a 20 year period, focusing on histological types, treatment modalities and outcomes.
MATERIALS AND METHODS: We identified patients who were diagnosed and treated for breast lymphoma at a single center from January 1995 to January 2014 and extracted data regarding patient demographics and clinical data.
RESULTS: Twenty-seven patients with breast lymphoma were identified, of which 3 were males. The median age at diagnosis was 37 years (range: 22-76 years). Chemotherapy was the main stay of treatment and 55.6% patients also received radiation to the affected breast. At our institute, only 3 patients, all with progressive disease, had surgery performed to achieve local palliation. Complete response after chemotherapy was seen in 63% patients and partial response in 7.4%, while 26% patients demonstrated disease progression. The mean follow up was 46.8 months. Seven patients (33.3%) who were alive at last follow up, as well as 1 patient who died, survived more than 5 years after diagnosis.
CONCLUSIONS: Patients with breast lymphoma should receive aggressive treatment, with combination of chemotherapy and radiation therapy. Surgery should be limited for diagnosis and palliation of local symptoms in cases of progressive disease.

Baloch AH, Khosa AN, Bangulzai N, et al.
Novel Nonsense Variants c.58C>T (p.Q20X) and c.256G>T (p.E85X) in the CHEK2 Gene Identified in Breast Cancer Patients from Balochistan.
Asian Pac J Cancer Prev. 2016; 17(7):3623-6 [PubMed] Related Publications
Breast cancer is very common and the leading cause of cancer deaths among women globally. Hereditary cases account for 510% of the total burden and CHEK2, which plays crucial role in response to DNA damage to promote cell cycle arrest and repair or induce apoptosis, is considered as a moderate penetrance breast cancer risk gene. Our objective in the current study was to analyze mutations in related to breast cancer. A total of 271 individuals including breast cancer patients and normal subjects were enrolled and all 14 exons of CHEK2 were amplified and sequenced. The majority of the patients (>95%) were affected with invasive ductal carcinoma (IDC), 52.1% were diagnosed with grade III tumors and 56.2% and 27.5% with advanced stages III and IV. Two novel nonsense variants i.e. c.58C>T (P.Q20X) and c.256G>T (p.E85X) at exon 1 and 2 in two breast cancer patients were identified, both novel and not reported elsewhere.

Zubair M, Hashmi SN, Afzal S, et al.
Immunohistochemical Expression of B Cell Lymphoma2 with Clinicopathological Correlation in Triple Negative Breast Cancers in Northern Pakistan.
Asian Pac J Cancer Prev. 2016; 17(7):3619-22 [PubMed] Related Publications
BACKGROUND: Triple negative breast cancers (TNBCs) are high grade aggressive tumors generally with a poor prognosis, not responding to hormonal and anti Her2 Neu therapy. Expression of the antiapoptotic B cell lymphoma 2 gene (Bcl2) is associated with low grade, slowly proliferating hormone receptor positive tumors with improved survival. Anti Bcl2 agents can be used as alternative targeted therapy in triple negative cancers.
MATERIALS AND METHODS: The objective of this study was to determine the immunohistochemical expression of Bcl2 in triple negative breast cancers and any correlation with clinicopathological variables in Northern Pakistan.
RESULTS: All 52 patients were females, aged between 28 and 80 years(average 48.0±12.1). 28 cases (53.8%) were positive for Bcl2, this being associated with low grade invasive ductal carcinomas, lymph node metastasis and lymphovascular invasion.
CONCLUSIONS: Bcl2 may be an important prognostic factor and its expression might be used for targeted therapy using Anti Bcl2 drugs.

Zaman MU, Fatima N, Zaman A, et al.
Significantly Low Effective Dose from 18FDG PET/CT Scans Using Dose Reducing Strategies: "Lesser is Better".
Asian Pac J Cancer Prev. 2016; 17(7):3465-8 [PubMed] Related Publications
BACKGROUND: Fluorodeoxyglucose (18FDG) PET/CT imaging has become an important component of the management paradigm in oncology. However, the significant imparted radiation exposure is a matter of growing concern especially in younger populations who have better odds of survival. The aim of this study was to estimate the effective dose received by patients having whole body 18FFDG PET/CT scanning as per recent dose reducing guidelines at a tertiary care hospital.
MATERIALS AND METHODS: This prospective study covered 63 patients with different cancers who were referred for PET/CT study for various indications. Patients were prepared as per departmental protocol and 18FDG was injected at 3 MBq/Kg and a low dose, nonenhanced CT protocol (LD NECT) was used. Diagnostic CT studies of specific regions were subsequently performed if required. Effective dose imparted by 18FDG (internal exposure) was calculated by using multiplying injected dose in MBq with coefficient 1.9?102 mSv/MBq according to ICRP publication 106. Effective dose imparted by CT was calculated by multiplying DLP (mGy.cm) with ICRP conversion coefficient "k" 0.015 [mSv / (mG. cm)].
RESULTS: Mean age of patients was 49 ±18 years with a male to female ratio of 35:28 (56%:44%). Median dose of 18FDG given was 194 MBq (range: 139293). Median CTDIvol was 3.25 (2.46.2) and median DLP was 334.95 (246.70 576.70). Estimated median effective dose imparted by 18FDG was 3.69 mSv (range: 2.855.57). Similarly the estimated median effective dose by low dose (nondiagnostic) CT examination was 4.93 mSv (range: 2.14 10.49). Median total effective dose by whole body 18FDG PET plus low dose nondiagnostic CT study was 8.85 mSv (range: 5.5613.00).
CONCLUSIONS: We conclude that the median effective dose from a whole body 18FDG PET/CT in our patients was significantly low. We suggest adhering to recently published dose reducing strategies, use of ToF scanner with CT dose reducing option to achieve the lower if not the lowest effective dose. This would certainly reduce the risk of second primary malignancy in younger patients with higher odds of cure from first primary cancer.

Shaikh F, Jamal Q, Baig S, et al.
Correlation of Hormone Receptor and HER2/neu Expression with Clinicopathologic Parameters in Primary Breast Tumors.
Asian Pac J Cancer Prev. 2016; 17(7):3363-7 [PubMed] Related Publications
BACKGROUND: Breast cancer (BC) is a major health issue worldwide as well as in Pakistan. All women belonging to any race, ethnicity or lineage are in danger of developing breast cancer. Significant factors influencing the development of breast malignancies are the genetic background, environmental conditions, reproductive parameters, the consequences of female hormones both intrinsic and extrinsic, alteration of immune status, and biologic determinants.
MATERIALS AND METHODS: Overall 150 biopsy proven patients were included in the study. Samples were submitted for histopathology and determination of estrogen and progesterone receptor expression and HER2/neu status. Associations with other characteristics like age, tumor stage, node involvement, histological grade were also studied.
RESULTS: Mean age at presentation was 46.7 years. The majority had invasive ductal carcinoma, 100 (84.7%), and were in stage pT3, 54 (45.7%). Important relationships (P<0.05) were found among ER, PR positivity, and Her 2 neu overexpression. However, no noteworthy link was identified amongst ER, PR, Her 2 neu and tumor grade, stage, age, lymph node involvement except for the menopausal status.
CONCLUSIONS: In summary, breast cancer patients featured an advanced stage of disease, more lymph node involvement, and moderately high grade tumors and with more estrogen, progesterone receptor and HER2 positive tumors.

Tabassum I, Mahmood H, Faheem M
Type 2 Diabetes Mellitus as a Risk Factor for Female Breast Cancer in the Population of Northern Pakistan.
Asian Pac J Cancer Prev. 2016; 17(7):3255-8 [PubMed] Related Publications
BACKGROUND: There has been much research work in the past to ascertain the association between type 2 diabetes mellitus and breast cancer, but definitive evidence has been scanty. The present study was carried out to determine the association of type 2 diabetes mellitus with breast cancer in the female population of Northern Pakistan.
MATERIALS AND METHODS: This casecontrol study was carried out in the Oncology Department of NORI Hospital. A total of 400 patients were included. Data were entered into PSPP 0.8.1. Twotailed significance tests were used and a pvalue of 0.05 was considered significant.
RESULTS: There were a higher percentage of postmenopausal women in the diabetic breast cancer patients' group as compared to the nondiabetic subset. The odds ratio for the association between diabetes and risk of developing breast cancer was elevated with statistical significance (OR = 2.96; 95 % CI =1.36.3; pvalue=0.004). The results of our study showed that diabetes is associated with a risk of developing breast cancer, especially in postmenopausal women (OR = 4.928; 95 % CI = 2.111.3; pvalue=0.001). The association was particularly marked in obese subjects (OR = 31.49; 95 % CI = 1.8 536; p value=0.01), as compared to nonobese subjects (OR = 0.642; 95 % CI = 0.21.7).
CONCLUSIONS: Diabetes is strongly associated with obesity and it tends to increase the risk of breast Cancer, especially in postmenopausal women. A highrisk subset for breast cancer comprised postmenopausal, diabetic and overweight women.

Qureshi MA, Khan S, Ujjan ID, et al.
Quantitative Analyses of Esophageal Cancer Research in Pakistan.
Asian Pac J Cancer Prev. 2016; 17(7):3117-22 [PubMed] Related Publications
BACKGROUND: Healthcare research is a neglected discipline in Pakistan and research related to esophageal cancer (ranks 9th in Pakistani males and 5th in females) is no exception in this regard. Particularly, there are no data available to delineate the overall status of esophageal cancer epidemiological studies in Pakistan. This study describes the first ever effort to make a systematic quantification, in an attempt to provide a roadmap to all stakeholders for designing appropriate epidemiological, diagnostic and therapeutic strategies.
MATERIALS AND METHODS: International (PubMed, ISI Web of Knowledge) and local (PakMedinet) scientific databases as well as Google search engine were searched using specified keywords to extract relevant publication. Well defined inclusion criteria were implemented to select publications for final analyses. All data were recorded by at least 3 authors and consensus data were entered into and analyzed for descriptive statistics (such as frequencies, percentages and annual growth rates) using Microsoft Excel and SPSS software.
RESULTS: A total of 79 publications fulfilled the inclusion criteria including 20 publications for which full texts were not available. Of the 79 publications, 59 (74.6%) were original/research publications, 5 (6.3%) were case reports, 4 (5.1%) were research communications, 2 (2.5%) were review articles, 1 was (1.2%) correspondence and 8 (10.1%) were un defined categories. Only 13 <20%) cities of Pakistan contributed towards the 79 publications. On average, only 1.9 relevant publications/year were published from 1976 (year of first publication) to the present. Alarmingly, a decline in the annual growth at 4.1% was recorded in the last six years.
CONCLUSIONS: Esophageal cancer research is largely unfathomed in Pakistan. Urgent/dramatic steps are required by all concerned to address this common (and under reported) cancer of Pakistan.

Majeed W, Iftikhar A, Khaliq T, et al.
Gastric Carcinoma: Recent Trends in Diagnostic Biomarkers and Molecular Targeted Therapies.
Asian Pac J Cancer Prev. 2016; 17(7):3053-60 [PubMed] Related Publications
Gastric cancer is generally associated with poor survival rates and accounts for a remarkable proportion of global cancer mortality. The prevalence of gastric carcinoma varies in different regions of world and across teh various ethnic groups. On the basis of pathological assessment, gastric cancer can be categorized as intestinal and diffuse carcinomas. The etiology is diverse, including chemical carcinogen exposure, and high salt intake Helicobacter pylori also plays a vital role in the pathogenesis of certain gastric carcinomas. The development of gastric cancer involves various alterations in mRNAs, genes (GOLPH3, MTA2) and proteins (Coronins). miRNAs, Hsamir135b, MiR21, miR106b, miR17, miR18a, MiR21, miR106b, miR17, miR18a and MiRNA375, miRNA1955p are the latest diagnostic biomarkers which can facilitate the early diagnosis of gastric carcinomas. Recent development in the treatment strategies for gastric carcinoma include the introduction of monoclonal antibodies, TKI inhibitors, inhibitors of PDGFR β, VEGFR1, VEGFR2, AntiEGFR and antiHER2 agents which can be applied along with conventional therapies.

Basra MA, Saher M, Athar MM, Raza MH
Breast Cancer in Pakistan a Critical Appraisal of the Situation Regarding Female Health and Where the Nation Stands?
Asian Pac J Cancer Prev. 2016; 17(7):3035-41 [PubMed] Related Publications
Breast cancer (BC) is the most common malignancy of women worldwide. In the past it was considered as disease of older middle aged women, but the incidence of BC in young females is growing in recent years concordant with studies in Pakistan. In this paper, we reviewed the mutant functions of tumor suppressor genes (BRCA1, BRCA2, p53, ATM and PTEN), epigenetic transformation and involvement of estrogen receptors in development of breast cancer. We further reviewed the current situation of BC in Pakistan that depicts a higher incidence in young females. According to SKMCH and RC data, age group 4549 years is more prone to BC with high rate of incidence 45.42%. A few studies explored the high expression of ER, PR and HER2/neu in Pakistani females. Moreover, presence of BRCA1 (c.1961dupA) mutation in Pakistani shows concordance with data in different areas of world. But we are unable to find an authentic study that can explore epigenetic based transformation of breast tumors in Pakistan. This area of research needs more attention to explore the complete picture of BC in Pakistan.

Bano S, Nazir S, Munir S, et al.
"Smart" nickel oxide based core-shell nanoparticles for combined chemo and photodynamic cancer therapy.
Int J Nanomedicine. 2016; 11:3159-66 [PubMed] Free Access to Full Article Related Publications
We report "smart" nickel oxide nanoparticles (NOPs) as multimodal cancer therapy agent. Water-dispersible and light-sensitive NiO core was synthesized with folic acid (FA) connected bovine serum albumin (BSA) shell on entrapped doxorubicin (DOX). The entrapped drug from NOP-DOX@BSA-FA was released in a sustained way (64 hours, pH=5.5, dark conditions) while a robust release was found under red light exposure (in 1/2 hour under λmax=655 nm, 50 mW/cm(2), at pH=5.5). The cell viability, thiobarbituric acid reactive substances and diphenylisobenzofuran assays conducted under light and dark conditions revealed a high photodynamic therapy potential of our construct. Furthermore, we found that the combined effect of DOX and NOPs from NOP-DOX@BSA-FA resulted in cell death approximately eightfold high compared to free DOX. We propose that NOP-DOX@BSA-FA is a potential photodynamic therapy agent and a collective drug delivery system for the systemic administration of cancer chemotherapeutics resulting in combination therapy.

Jabeen S, Qureshi MZ, Attar R, et al.
How sesquiterpenes modulate signaling cascades in cancers.
Cell Mol Biol (Noisy-le-grand). 2016; 62(7):110-7 [PubMed] Related Publications
Data obtained from high-throughput technologies has started to shed light on the interplay between signal transduction cascades and chromatin modifications thus adding another layer of complexity to the already complex regulation of the protein network. Based on the insights gleaned from almost a decade of research, it has now been convincingly revealed that sesquiterpenes effectively modulated different intracellular signaling cascades in different cancers. In this review we summarize how sesquiterpenes mediated Wnt, Shh, Notch and TRAIL induced signaling cascades.

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