Rhabdomyosarcoma - an Epidemiological and Histopathologic Study of 277 Cases from a Major Tertiary Care Center in Karachi, Pakistan

Ahmad, Zubair,Din, Nasir Ud,Ahmad, Arsalan,Imran, Sheharbano,Pervez, Shahid,Ahmed, Rashida,Kayani, Naila Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Aim: To present the epidemiologic data (age, gender, size etc) and histopathologic and immunohistochemical features of cases of rhabdomyosarcoma (RMS) reported in our department. Settings: Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan. Duration: All cases of RMS diagnosed between January 1, 2003 and December 31, 2012 were included in the study. Results: A total of 277 cases were included. Embryonal rhabdomyosarcoma (ERMS) was by far the dominant histologic type (87.4%) followed by alveolar type (ARMS)(9.4%). ERMS was much more common in males (64.0%)and over 65% of cases occurred in the first decade of life (over 90% in the first two decades). Head and neck region was commonest site for ERMS (46.7%), followed by the genitourinary system (16.1%). Over 65% cases of ARMS occurred in the extremities. Over 80% cases of ARMS occurred in the first 3 decades of life. Immunohistochemical staining for Desmin and MyoD1 was positive in 96.7% and 85.4% respectively. Conclusions: The epidemiologic data and microscopic findings in our patients are similar to international published data on rhabdomyosarcoma.

Effects of Rapamycin on Cell Apoptosis in MCF-7 Human Breast Cancer Cells

Tengku Din, Tengku Ahmad Damitri Al-Astani,Seeni, Azman,Khairi, Wirdatul-Nur Mohd,Shamsuddin, Shaharum,Jaafar, Hasnan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remains unclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using MCF-7 breast cancer cells. Materials and Methods: MCF-7 cells were plated at a density of $1{\times}10^5$ cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at $37^{\circ}C$, 5% $CO_2$ and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads. Results: Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The $IC_{50}$ value of rapamycin on the MCF-7 cells was determined as $0.4{\mu}g/ml$ (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively. Conclusions: This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent.

Rapamycin and PF4 Induce Apoptosis by Upregulating Bax and Down-Regulating Survivin in MNU-Induced Breast Cancer

Al-Astani Tengku Din, Tengku Ahmad Damitri,Shamsuddin, Shazana Hilda,Idris, Fauziah Mohamad,Wan Mansor, Wan Nor Ariffin,Abdul Jalal, Muhammad Irfan,Jaafar, Hasnan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.9

Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70mg/kg body weight. The rats were treated when the tumors reached the size of $14.5{\pm}0.5mm$ and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of $20{\mu}g$/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin. Results: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p). Conclusions: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.

Epidemiologic Data, Tumor Size, Histologic Tumor Type and Grade, Pathologic Staging and Follow Up in Cancers of the Ampullary Region and Head of Pancreas in 311 Whipple Resection Specimens of Pakistani Patients

Ahmad, Zubair,Ud Din, Nasir,Minhas, Khurram,Moeen, Sarosh,Ahmed, Arsalan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17

Aim: To report the histologic findings on Whipple resection specimens and thus determine the extent and spread of carcinomas of ampullary region and head of pancreas in our population. Setting: Section of Histopathology, Department of Pathology, Aga Khan University Hospital (AKUH), Karachi, Pakistan. Materials and Methods: A case series of 311 consecutive Whipple resection specimens received between January 1,2003 and December 31, 2014. Specimens processed for histologic sections and representative sections submitted and histologically examined as per established and standard protocols. All relevant tumor parameters including histologic type, histologic grade, pathologic T and N stage and tumor size were assessed. Epidemiologic data were also recorded. All findings were analysed using SPSS 19.0 software. Results: Ampullary (periampullary) carcinomas were much more common than carcinomas of the head of the pancreas, especially in males, with an average age of 53 years. Mean tumor size was 2.5 cms, over 54% were well differentiated. A large majority were pT2 or pT3 and N0. Carcinomas of pancreatic head were also more common in males, mean age was 55 years, mean tumor size was 3.5cms, and over 65% were moderately differentiated. The majority were T2 or T3 and pN1. Prognostically, significant statistical correlation was seen with tumor grade and pathologic T and N stage (p values statistically significant). However, tumor size was not statistically significant. Conclusions: Ampullary carcinomas are more common compared to pancreatic carcinomas. Majority of ampullary carcinomas were well differentiated while majority of pancreatic carcinomas were moderately differentiated. Large majority of both types of cases were pT2 or T3. Histologic tumor grade and pathologic T and N stage are significantly related to prognosis in Pakistani patients with ampullary and pancreatic cancers.

Toward modeling and optimization of features selection in Big Data based social Internet of Things

Ahmad, Awais,Khan, Murad,Paul, Anand,Din, Sadia,Rathore, M. Mazhar,Jeon, Gwanggil,Choi, Gyu Sang North-Holland 2018 Future generations computer systems Vol.82 No.-

<P><B>Abstract</B></P> <P>The growing gap between users and the Big Data analytics requires innovative tools that address the challenges faced by big data volume, variety, and velocity. Therefore, it becomes computationally inefficient to analyze and select features from such massive volume of data. Moreover, advancements in the field of Big Data application and data science poses additional challenges, where a selection of appropriate features and High-Performance Computing (HPC) solution has become a key issue and has attracted attention in recent years. Therefore, keeping in view the needs above, there is a requirement for a system that can efficiently select features and analyze a stream of Big Data within their requirements. Hence, this paper presents a system architecture that selects features by using Artificial Bee Colony (ABC). Moreover, a Kalman filter is used in Hadoop ecosystem that is used for removal of noise. Furthermore, traditional MapReduce with ABC is used that enhance the processing efficiency. Moreover, a complete four-tier architecture is also proposed that efficiently aggregate the data, eliminate unnecessary data, and analyze the data by the proposed Hadoop-based ABC algorithm. To check the efficiency of the proposed algorithms exploited in the proposed system architecture, we have implemented our proposed system using Hadoop and MapReduce with the ABC algorithm. ABC algorithm is used to select features, whereas, MapReduce is supported by a parallel algorithm that efficiently processes a huge volume of data sets. The system is implemented using MapReduce tool at the top of the Hadoop parallel nodes with near real-time. Moreover, the proposed system is compared with Swarm approaches and is evaluated regarding efficiency, accuracy and throughput by using ten different data sets. The results show that the proposed system is more scalable and efficient in selecting features.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Presents an architecture for Social Internet of Things. </LI> <LI> Modeling and optimization of Big Data. </LI> <LI> System architecture based on ABC. </LI> <LI> MapReduce with ABC to enhance system efficiency. </LI> </UL> </P>

A Novel Compact Ultra-Wideband Frequency-Selective Surface-Based Antenna for Gain Enhancement Applications

Din Iftikhar Ud,Ullah Waheed,Abbasi Nisar Ahmad,Ullah Sadiq,Shihzad Waleed,Khan Bilawal,Jayakody Dushantha Nalin K. 한국전자파학회 2023 Journal of Electromagnetic Engineering and Science Vol.23 No.2

This article presents a compact ultra-wideband (UWB) circular monopole antenna with a frequency-selective surface (FSS) for gain enhancement. The proposed antenna has a circular patch with circular cuts at the edges and is excited by a microstrip feed. The bottom plane is truncated and further modified by two triangular cuts at the sides and one rectangular cut in the middle to improve the radiation characteristics of the UWB antenna. The antenna is designed on an FR-4 substrate with a thickness of 1.6 mm, a relative permittivity of 4.3, and planner dimensions of 30 mm × 30 mm. To improve the proposed antenna’s gain, an FSS is designed that consists of periodic unit cells of metal printed on the upper layer of an FR-4 substrate with dimensions of 0.11λ × 0.11λ at the lowest operating frequency of 3.3 GHz. The FSS shows a very low transmission coefficient and linearly reducing reflection phase with increasing frequency over a frequency range of 3.3–10.8 GHz. The gain of the proposed antenna is increased from 3 dB to 8.1 dB at 9 GHz by placing the antenna on the FSS. Moreover, the prototype of the proposed antenna is fabricated, and the experimental results are measured, which show close agreements with simulated results. The FSS-based antenna has directional radiation patterns, making it a potential candidate for ground-penetrating radar and UWB applications.

Gastrointestinal Stromal Tumors: A Clinicopathologic and Risk Stratification Study of 255 Cases from Pakistan and Review of Literature

Din, Nasir Ud,Ahmad, Zubair,Arshad, Huma,Idrees, Romana,Kayani, Naila Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.12

Purpose: To describe the clinicopathological features of gastrointestinal stromal tumors (GIST) diagnosed in our section and to perform risk stratification of our cases by assigning them to specific risk categories and groups for disease progression based on proposals by Fletcher et al and Miettinen and Lasota. Materials and Results: We retrieved 255 cases of GIST diagnosed between 2003 and 2014. Over 59% were male. The age range was 16 to 83 years with a mean of 51 years. Over 70% occurred between 40 and 70 years of age. Average diameter of tumors was 10 cms. The stomach was the most common site accounting for about 40%. EGISTs constituted about 16%. On histologic examination, spindle cell morphology was seen in almost of 85% cases. CD117 was the most useful immunohistochemical antibody, positive in 98%. Risk stratification was possible for 220 cases. Based on Fletcher's consensus proposal, 62.3 gastric, 81.8% duodenal, 68% small intestinal, 72% colorectal and 89% EGISTs were assigned to the high risk category; while based on Miettinen and Lasota's algorithm, about 48% gastric, 100% duodenal, 76% small intestinal, 100% colorectal and 100% EGISTs in our study were associated with high risk for disease progression, tumor metastasis and tumor related death. Follow up was available in 95 patients; 26 were dead and 69 alive at follow up. Most of the patients who died had high risk disease and on average death occurred just a few months to a maximum of one to two years after initial surgical resection. Conclusions: Epidemiological and morphologic findings in our study were similar to international published data. The majority of cases in our study belonged to the high risk category.

Developing an efficient in vitro callusing and regeneration protocol in Dendranthema × grandiflorum Kitam.

Din Ambreena,Qadri Z. A.,Wani Muneeb Ahmad,Iqbal Shameen,Malik Sajid Ali,Bhat Z. A.,Banday Neelofar 한국작물학회 2022 Journal of crop science and biotechnology Vol.25 No.4

To standardize the methodology for in vitro callusing and regeneration of two chrysanthemum cultivars, ‘Candid’ and ‘Flirt,’ an experiment was carried out. The petals and leaf segments were used as explants. In both cultivars, petals were shown to be the most effective for callusing and regeneration. In both cultivars, MS medium enriched with 1.00 mg L−1 BAP + 1.50 mg L−1 NAA resulted in the best callusing of petal explants in terms of minimal days to callus initiation, maximal callus induction, and callus weight per explant. When using petal explants from both cultivars, the shortest time (13.25 and 16.00 days) to callus initiation, the highest callus induction (91.66 and 83.33%) and the highest mean callus weight (2.43 and 2.31 g per explant) were all found in media augmented with 1.00 mg L−1 BAP + 1.50 mg L−1 NAA. In both cultivars, MS media supplied with 1.00 mg L−1 Kinetin + 0.50 mg L−1 IAA resulted in the best regeneration of petal explants in calli-producing shoots and shoot number per explant. Maximum calli-producing shoots 89.58 and 87.49% and significantly maximum shoot number 3.25 and 2.75 per explant were noticed in media fortified with Kinetin 1.00 mg L−1 + IAA 0.50 mg L−1 in case of petal explants of both the cultivars. Nevertheless, the finest callusing of leaf explants in terms of minimum days to callus initiation, highest callus induction in both cultivars was achieved using MS media supplied with 1.00 mg L−1 BAP + 1.50 mg L−1 NAA, whereas the highest callus weight per explant was acquired using MS media supplied with 0.50 mg L−1 BAP and 2.50 mg L−1 NAA. Explants from both cultivars showed a minimum callus initiation period of 15.25 and 16.75 days, callus induction rates of 89.57 and 81.24%, and maximum mean callus weights of 0.94 and 0.89 g, correspondingly.

Central, Extraventricular and Atypical Neurocytomas: a Clinicopathologic Study of 35 Cases from Pakistan Plus a Detailed Review of the Published Literature

Ahmad, Zubair,Din, Nasir Ud,Memon, Aisha,Tariq, Mohammad Usman,Idrees, Romana,Hasan, Sheema Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called "extraventricular neurocytomas". A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as "atypical neurocytomas. Aim: The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors. Materials and Methods: We retrieved and reviewed 35 cases diagnosed between 2001 and 2015. Results: Sixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer-Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.

Gastrointestinal, Liver and Biliary Tract Pathology: A Histopathological and Epidemiological Perspective from Pakistan with a Review of the Literature

Ahmad, Zubair,Arshad, Huma,Fatima, Saira,Idrees, Romana,Ud-Din, Nasir,Ahmed, Rashida,Ahmed, Arsalan,Memon, Aisha,Minhas, Khurram,Arif, Muhammad,Fatima, Samia,Haroon, Saroona,Pervez, Shahid,Hasan, Shee Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Aim: To present an epidemiological and histological perspective of diseases of the gastrointestinal tract (including liver and biliary tract) at the Section of Histopathology, Department of Pathology, AKUH, Karachi, Pakistan. Materials and Methods: All consecutive endoscopic biopsies and resections between October 1 and December 31, 2012 were included. Results: A total of 2,323 cases were included. Carcinoma was overwhelmingly the commonest diagnosis on esophageal biopsies (69.1%); chronic helicobacter gastritis (45.6%) followed by adenocarcinoma (23.5%) were the commonest diagnoses on gastric biopsies; adenocarcinoma (27.3%) followed by ulcerative colitis (13.1%) were the commonest diagnoses on colonic biopsies; acute appendicitis (59.1%) was the commonest diagnosis on appendicectomy specimens; chronic viral hepatitis (44.8%) followed by hepatocellular carcinoma (23.4%) were the commonest diagnoses on liver biopsies; chronic cholecystitis was the commonest diagnosis (over 89%) on cholecystectomy specimens. Conclusions: Squamous cell carcinoma comprised 88.8% of esophageal cancers. About 67% were in the lower third and 56.5% were moderately differentiated; mean ages 49.8 years for females and 55.8 years for males; 66% cases were from South West Pakistan. Over 67% patients with gastric adenocarcinoma were males; mean ages 59 and 44 years in males and females respectively, about 74% gastric carcinomas were poorly differentiated; and 62.2% were located in the antropyloric region. About 63% patients with colorectal adenocarcinoma were males; mean ages 46.1 and 50.5 years for males and females respectively; tumor grade was moderately differentiated in 54%; over 80% were located in the left colon. In 21.2% appendicectomies, no acute inflammation was found. Acute appendicitis was most common in young people. Hepatitis C (66.3%) was more common than hepatitis B (33.7%); about 78% cases of hepatocellular carcinoma occurred in males; females comprised 76.7% patients with chronic cholecystitis; and 77.8% patients with gall bladder carcinoma. All resection specimens showed advanced cancers. Most cancers occurred after the age of 50 years.