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Education is human’s problem. Human is a dynamic creature. The dynamics of human’s life demands dynamic educational process in order to fulfill human’s needs. In order to maintain the dynamic thoughts of Islamic education, some relevant studies are needed. Revelation based Islamic education studies can develop the concept of Islamic education and avoid the possible mistakes made by researchers in education fields. In doing so, the researchers may use tafsir thematic approach. This is made possible since al-Quran contains much information concerning with education and guides and leads any activities of man’s thoughts into those which are suitable of Islamic teaching as well. Kata kunci: pengembangan pemikiran, pendidikan islam, tafsir tematik

Objectives: To identify and analyse the different types and frequencies of morphological pattern in endometrial biopsies along with their associated diagnoses across different age groups., Methods: The cross-sectional study was conducted at the Histopathology Section of the Dow Diagnostics Reference and Research Laboratory, Dow University Health Sciences, Karachi, from October 2022 to October 2023. Data was obtained from pre-existing medical record of samples of endometrial biopsies. Open Epi sample size calculator is used for the estimation of sample size. The patients were divided into two aged-based groups; reproductive age ≤45 years in group 1 and postmenopause age ≥46 years in group 2. The histological diagnosis was made by a consultant histopathologist., Results: Of the 430 endometrial biopsies 222(51.6%) were in group 1 and 208(48.4%) were in group 2. In both groups, the most common finding was polyps 271(63%). Malignant changes were found in 12(5.7%) group 2 cases compared to 4(1.8%) group 1 cases., Conclusions: The most common endometrial lesion in both age groups was endometrial polyp. Malignant changes were seen more in postmenopausal women compared to those in the reproductive age group.

Background: Despite a high incidence of colorectal carcinoma, data regarding genetic aberrations in colorectal carcinoma (CRC) patients in Pakistan is scarce. This study aimed to determine the frequency of BRAFV600E mutations in colorectal carcinoma tissue in the Pakistani population and to associate BRAFV600E expression with CD133, a marker of colorectal stem cells, and CDX2 marker of differentiation., Methods: Sanger Sequencing of exon 15 (426 bp) including the hotspot V600E was performed on formalin-fixed-paraffin-embedded (FFPE) CRC tissue samples of 115 patients. The samples were subjected to immunohistochemistry (IHC) to assess the expression of BRAFV600E, CDX2, and CD133. Additionally, homology modelling and docking were performed to investigate novel deletions revealed in sequencing., Results: Twenty-four (20.8%) BRAF variants were identified in the coding region, with V600E mutations detected in 14 (12.2% )cases (GenBank: PP003258.1; Pop Set: 2678087296). Moreover, a wide spectrum of novel non-V600E mutations (8.6%) were identified, including deletions and missense variations. In-silico analysis revealed that due to large deletions in the coding region of three samples, the affinity of the anti-BRAF drugs (Encorafenib and Vemurafenib) for the active site decreased in comparison to the wild type. The IHC analysis showed that BRAFV600E expression was significantly associated with CD133 expression (χ 2 (1, n=115)  = 26.351; p = < 0.001) and with CDX2 expression (χ 2 (1, n=115)  = 14.88; p = 0.001). Multivariate analysis using binary logistic regression revealed association of BRAFV600E mutations with age (OR = 1.123; CI = 1.024-1.232; p = 0.014), gender (OR = 0.071; CI = 0.006-0.831; p = 0.035), grade (0.007; CI = 0-0.644) and CD133 expression (OR = 65.649; CI = 2.153-2001.556; p = 0.016)., Conclusion: The present study demonstrates a notably high V600E frequency (12.2%) in comparison to global reported data, which ranges from 0.4 to 18%. This finding reflects the importance of upfront BRAF testing of the genetically distinct population of Pakistan. Previously unreported mutations identified in the sample may be of clinical significance and warrant further investigation. The concomitant high expression and significant association between CD133 and BRAFV600E represent vital actionable genes that may be targeted together to improve CRC patient management., (© 2024. The Author(s).)

Introduction Microsatellite instability (MSI) is an important pathway in colorectal carcinoma (CRC) pathogenesis. MSI occurs due to mutations in mismatch repair (MMR) genes that include MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6). CRC with MSI is termed MMR deficient (dMMR) CRC. Conversely, CRC with intact MMR genes is called microsatellite stable (MSS) or MMR proficient (pMMR). In this study, we compared the clinicopathological features of dMMR CRC with pMMR CRC. Methods It was a retrospective study conducted in the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, from March 2020 to February 2022, over a duration of two years. Biopsy-proven cases of CRC with upfront surgical resection were included in the study. Microscopic examination was performed to evaluate tumor type, grade, and extent of invasion, presence of necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), peritumoral lymphocytes (PTL), intratumoral lymphocytes (ITL), and nodal metastasis. Immunohistochemical staining was performed using antibodies, namely, MLH1, PMS2, MSH2, and MSH6. Any loss of nuclear expression in tumor cells was termed dMMR or microsatellite instable, whereas the intact nuclear expression in tumor cells was labeled as MSS or pMMR. Results A total of 135 cases of CRC were included in the study. The mean age at diagnosis was 46.76 ± 17.74 years, with female predominance (60.7%). The loss of MLH1, PMS2, MSH2, and MSH6 expression was noted in 39.3%, 34.1%, 17.8%, and 16.3% cases, respectively. Overall, 59.3% of CRCs were pMMR, while 40.7% were dMMR. A significant association of MMR status was noted with respect to age, PNI, LVI, tumor grade, tumor (T) and nodal (N) stage, mucinous differentiation, and ITL. dMMR CRC was significantly above 50 years than pMMR CRC. The frequency of PNI and LVI was lower in dMMR CRC than in pMMR CRC. Conversely, the higher grade (grade 3) and higher T-stage (T4) were associated with dMMR CRC. Alternatively, the frequency of higher N stage (N2b) was more commonly seen in pMMR CRC. Moreover, mucinous differentiation and ITL were significantly associated with dMMR CRC. Conclusion A significant proportion of CRC patients in our population demonstrated dMMR status. dMMR CRC had a higher histological grade with a higher frequency of mucinous differentiation and higher T-stage. Conversely, the presence of LVI, PNI, and higher N stages were associated with pMMR CRC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hashmi et al.)

Introduction:  Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck region, commonly termed as head and neck squamous cell carcinoma (HNSCC). Data related to biomarker expression in HNSCC are scarcely available, especially in our population. This study aimed to evaluate the association of immunohistochemical (IHC) expression of p16, epidermal growth factor receptor (EGFR), p27, and p53 in HNSCC with clinical and pathological parameters., Methods:  This retrospective cross-sectional study was conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan from February 2017 to January 2022. A total of 308 cases of HNSCC with upfront surgical resection were included in the study. IHC analysis was performed for EGFR, p16, p27, and p53, and association with clinicopathological parameters was sought., Results:  p16, EGFR, and p53 positivity were noted in 22.1%, 18.8%, and 66.2% cases, respectively, whereas loss of p27 expression was seen in 14.3% cases of HNSCC. A significant association of p16 expression was observed with age, tumor size, tumor site, nodal metastasis, extranodal extension (ENE), and perineural invasion (PNI). Cases aged over 50 years were more significantly associated with positive p16. Similarly, cases with oral cavity SCC were more significantly associated with positive p16. HNSCC with larger tumor size, the presence of nodal metastasis, and ENE and PNI were associated with negative p16 expression. Similarly, a significant association of EGFR expression was observed with age, tumor size, tumor site, histological subtype, histological differentiation, nodal metastasis, ENE, and PNI (p < 0.05). Cases of HNSCC with age less than 50 years were associated with positive EGFR expression. Similarly, oral cavity and lip SCCs were associated with positive EGFR expression compared with other sites. Moreover, positive EGFR expression was significantly associated with nodal metastasis, ENE, moderate histological differentiation, and the presence of PNI. Loss of p27 expression was significantly associated with nodal stage and ENE; low nodal stage and absence of ENE were associated with p27 loss of expression, whereas no significant association was seen with other pathological parameters. Alternatively, a significant association of mutant-type p53 expression was noted with gender, nodal stage, and histological subtype. Females with HNSCC show a higher frequency of mutant-type p53 expression than males. Moreover, higher nodal stage (N2b and higher) and non-keratinizing SCCs were significantly associated with mutant-type p53 expression., Conclusion:  Our study found a high expression of EGFR and mutant-type p53 expression in HNSCC. Conversely, p16 expression and loss of p27 expression were low. Moreover, EGFR and mutant-type p53 expression were associated with poor pathological parameters, whereas p16 expression was associated with better histological features., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hashmi et al.)

Background: Microscopic colitis (MC) is one of the most underdiagnosed conditions leading to chronic watery diarrhoea in patients worldwide. This is the first study of this kind in Pakistan and we aimed to calculate the frequency as well as study the risk factors behind the disease., Methods: This was a prospective cross-sectional study in a tertiary care hospital in Pakistan. A total of 58 participants with chronic watery diarrhoea who had normal colonoscopy were recruited for the study and biopsies were obtained for diagnosing MC., Results: 2 participants out of 58 (3.4%) had biopsy proven microscopic colitis; one patient had a lymphocytic colitis variant and the other had a collagenous colitis variant. The average score based on the MC scoring system was 7.53 in the entire study group. The patient with lymphocytic colitis had a score of 06 while the patient with collagenous colitis had a score of 8., Conclusions: The frequency of microscopic colitis was found to be 3.4% of all cases of chronic watery diarrhoea. A link between MC and autoimmune diseases was also observed. However, we had a limited sample size and encouraged future studies to employ a larger sample size to get a multifaceted look at the disease process.

Background Breast cancer is a heterogeneous disease with many histological and molecular/intrinsic breast cancer subtypes. Intrinsic breast cancer subtypes include luminal A, luminal B, human epidermal growth factor receptor 2 (HER2/neu), and triple-negative subtypes. The intrinsic breast cancer typing is based on the expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki67-labeling index. One of these patients' foremost prognostic factors upon surgical resection is a response to neoadjuvant chemotherapy. The presence of a pathologically complete response (pCR) indicates a favorable patient outcome compared with a pathologically partial response (pPR). In this study, we compared the neoadjuvant chemotherapy response in breast cancer in different intrinsic breast cancer subtypes. Methodology It was a retrospective cross-sectional study conducted in the Department of Histopathology, Liaquat National Hospital, from January 2019 to December 2022, over three years. A total of 287 post-neoadjuvant chemotherapy cases of breast cancer were included. Anthracyclines and taxanes, coupled with or without anti-HER2/neu therapy, have been used in the neoadjuvant chemotherapy treatment setting contingent upon the patients' HER2/neu status. The post-chemotherapy response was assessed pathologically and categorized into pCR and pPR. Results The mean age of the patients was 47.90 ± 10.34 years, with a mean tumor size and Ki67 index of 5.36 ± 2.59 cm and 36.30 ± 22.14%, respectively. Invasive breast carcinoma of no special type (IBC-NST) made up 88.2% of cases, while grade 2 carcinomas made up 45.5%. The majority of tumors (42.7%) belonged to tumor (T) stage T2, and nodal metastasis was detected in 59.7% of patients. The intrinsic breast cancer subtypes luminal B (40.6%) and triple negative (33.3%) were the most prevalent, followed by luminal A (15.8%) and HER2/neu (10.3%). In 81 cases (24.5%), pCR was detected. The association of post-neoadjuvant chemotherapy response with intrinsic breast cancer subtypes showed a significant difference ( P  < 0.001). The highest frequency of pCR was noted in HER2/neu cancers (58.8%), followed by luminal B (25.4%) and triple negative (23.6%). Regarding age, T-stage, tumor grade, and histological type of carcinoma, there was no discernible difference between pCR and pPR. Conversely, a significant association was noted for the Ki67 index. A Ki67 index higher than 25% showed a significantly higher frequency of pCR. Conclusions In postchemotherapy specimens, the HER2/neu breast cancer subtype substantially displayed higher pCR, followed by luminal B and triple-negative subtypes. After identifying the patients' subtypes, intrinsic subtyping can help determine the prognosis and anticipated response to chemotherapy. Furthermore, prechemotherapy breast specimens with high Ki67 index values have shown a direct association with neoadjuvant chemotherapy response., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hashmi et al.)

Background: Identification of gene targets and biological pathways involved in colorectal carcinoma (CRC) is essential for better management of patients. Our study aims to highlight common somatic mutations in colorectal carcinoma and to identify dysregulated pathways and gene enrichment based on KRAS and BRAF interaction network analysis., Methods: By using cancer browser tool in COSMIC database, mutation frequencies of the top 20 mutated genes listed for colorectal adenocarcinoma were identified. The most frequent variants of selected genes were explored with ClinVar database which led to identification of protein change along with its cytogenic location, variant type, variant length and the associated single nucleotide polymorphism (SNP). These identified SNPs were searched in Pakistani database using 1000genome in an attempt to identify common polymorphisms. Using the database ClinicalTrial.gov the number of clinical trials based upon these selected mutations was explored. Enrichment and protein interaction (PI) analysis of KRAS and BRAF was carried out to reveal significant biological pathways associated with these genes., Results: In cumulative data, among all variants about 57% of substitution mutations are observed to be G>A including mutations in KRAS, Tp53, SMAD4, PI3K and NRAS. The mutations of KRAS (c.35G>A), TP53 (c.524G>A) and APC (c.4348C>T) were found to be pathogenic with single nucleotide variation and variant length of 1bp. Searching 1000genome database revealed that 100 % of alleles found in East Asian population studied are 'C'(frequency=1). Significant biological pathways (<0.05) identified by our search include Trk receptor signalling mediated by the MAPK pathway, signalling to p38 via RIT and RIN, signalling to ERKs, Frs2-mediated activation, ARMS-mediated activation and prolonged ERK activation events., Conclusions: Our study highlights the role of genetic profiling in CRC, with emphasis on mutations which may define treatment outcome. Targeting several collateral pathways simultaneously may be further explored to improve colorectal cancer therapeutics.

Cancer is an uncontrolled, abnormal growth of cells and the second cause of death after cardiovascular disease. At present, chemotherapy and related drugs have three major categories. All three have characteristic action and toxicity levels of antitumor activity. Due to indications of unwanted side effects, the exploration of novel and selective anticancer agents is crucially required. Heterocyclic compounds have always played a major role in research for new drug discovery and development. 1,3,4-oxadiazole derivatives are heterocyclic isomers having pharmacological properties and play an important role as antiproliferative agents. The present review summarizes anticancer activities of 1,3,4-oxadiazole derivatives against different cell lines, such as HCT-116, MCF-7, HeLa, SMMC-7721, and A549. The results showed that 1,3,4-oxadiazole and its derivatives have the potential to play a major role as an anticancer agent with fewer side effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: 1. Identification of protein expression and subcellular localization of E-cadherin (E-cad), p120 catenin (P120ctn), and Kaiso in oral cancer (OC). 2. To study the protein expression of cyclin D1 and c-Myc (Kaiso targets) and determine their relationship with the expression and localization of Kaiso., Methods: Histological grading was performed in accordance with Broder's criteria. Expression and localization data for E-cad, p120ctn, Kaiso, cyclin D1, and c-Myc were acquired using immunohistochemistry. Data were analyzed using SPSS version 21. The chi-square test was used to measure the statistical significance of associations, with p  < 0.05 as statistically significant., Results: Of 47 OC cases, 36% showed low E-cad expression and 34% showed low p120ctn. Low Kaiso expression was recognized in 78% of tumor specimens. Aberrant cytoplasmic localization of p120ctn was seen in 80.8% cases. Cytoplasmic Kaiso localization was appreciated in 87% of tumor tissues, whereas 29.7% lacked any nuclear Kaiso. Kaiso expression was significantly associated with the expression of cyclin D1 but not with c-Myc., Conclusion: The present study identified a change in the localization of Kaiso in OC. The significance of this in relation to OC and tumor prognosis needs to be investigated with further studies using larger sample sizes and more sensitive molecular tools., (© 2022 [The Author/The Authors].)

Background: A group of genetically altered cells that have not transformed into a clinical or histologically identifiable state of malignancy but contains a higher risk of transforming into one is known as the field of cancerization. Numerous molecules are being investigated for their significance in the development of this phenomenon. One such protein of this family is Kaiso also known as ZBTB33 (Zinc Finger and BTB Domain containing 33). This protein belongs to the POZ-ZF family of transcription factors and may have functional tasks similar to its other siblings such as the growth and development of vertebrates and the pathogenesis of neoplastic diseases. Nevertheless, its role in the pathogenesis, progression, epithelial mesenchyal transition and field cancerization in case of oral cancer still needs exploration. Hence, this study was designed to explore the expressional differences between the mucosa of controls and those diagnosed with oral squamous cell carcinoma (OSCC)., Methods: Soft tissue samples were obtained from the main tumor, tumor periphery and opposite buccal mucosa of 50 oral cancer patients, whereas normal mucosa was taken from 50 volunteers undergoing elective tooth removal. The acquired samples were subjected to Immunohistochemical exploration for expression of Kaiso and E-Cadherin. The expression was measured using Image-J IHC profiler and summed as Optical density. The Optical density values were then subjected to statistical analysis., Results: Results revealed a significant differential expression of Kaiso between the mucosal tissues taken from oral cancer patients and controls (p-value: < 0.0001), showing almost 50% down-regulation of Kaiso in all three tissue samples taken from oral cancer patients as compared to normal mucosa., Conclusion: Kaiso has a significant difference of expression in the mucosa of oral cancer patients as compared to the mucosa of normal patients, making it a probable contributor to disease pathogenesis and field cancerization., (© 2022. The Author(s).)

Background: This study assesses the feasibility of producing hyperimmune anti-COVID-19 intravenously administrable immunoglobulin (C-IVIG) from pooled convalescent plasma (PCP) to provide a safe and effective passive immunization treatment option for COVID-19. Materials & methods: PCP was fractionated by modified caprylic acid precipitation followed by ultrafiltration/diafiltration to produce hyperimmune C-IVIG. Results: In C-IVIG, the mean SARS-CoV-2 antibody level was found to be threefold (104 ± 30 cut-off index) that of the PCP (36 ± 8.5 cut-off index) and mean protein concentration was found to be 46 ± 3.7 g/l, comprised of 89.5% immunoglobulins. Conclusion:  The current method of producing C-IVIG is feasible as it uses locally available PCP and simpler technology and yields a high titer of SARS-CoV-2 antibody. The safety and efficacy of C-IVIG will be evaluated in a registered clinical trial (NCT04521309).

Objective: The proinflammatory cytokine S100A12 is associated with coronary atherosclerotic plaque rupture. We previously generated transgenic mice with vascular smooth muscle-targeted expression of human S100A12 and found that these mice developed aortic aneurysmal dilation of the thoracic aorta. In the current study, we tested the hypothesis that S100A12 expressed in vascular smooth muscle in atherosclerosis-prone apolipoprotein E (ApoE)-null mice would accelerate atherosclerosis., Methods and Results: ApoE-null mice with or without the S100A12 transgene were analyzed. We found a 1.4-fold increase in atherosclerotic plaque size and more specifically a large increase in calcified plaque area (45% versus 7% of innominate artery plaques and 18% versus 10% of aortic root plaques) in S100A12/ApoE-null mice compared with wild-type/ApoE-null littermates. Expression of bone morphogenic protein and other osteoblastic genes was increased in aorta and cultured vascular smooth muscle, and importantly, these changes in gene expression preceded the development of vascular calcification in S100A12/ApoE-null mice. Accelerated atherosclerosis and vascular calcification were mediated, at least in part, by oxidative stress because inhibition of NADPH oxidase attenuated S100A12-mediated osteogenesis in cultured vascular smooth muscle cells. S100A12 transgenic mice in the wild-type background (ApoE+/+) showed minimal vascular calcification, suggesting that S100A12 requires a proinflammatory/proatherosclerotic environment to induce osteoblastic differentiation and vascular calcification., Conclusions: Vascular smooth muscle S100A12 accelerates atherosclerosis and augments atherosclerosis-triggered osteogenesis, reminiscent of features associated with plaque instability.

Objective: To evaluate the frequency and types of thyroid carcinoma with respect to age and sex groups., Methods: This was a retrospective study conducted at the Department of Pathology, Basic Medical Sciences Institute, Jinnah postgraduate medical centre Karachi. A total of 998 thyroid lesions over a period of 05 years, from July 2000 to June 2005 were reviewed. H and E slides were studied to determine the types and frequencies of malignant lesions of thyroid. Special stains were performed whenever required., Results: A total of 998 thyroid lesions were reviewed, of which 153 were found to be malignant. Papillary carcinoma was the commonest malignant lesion with a frequency of 90.2% followed by 4.5% medullary carcinoma, 2% follicular carcinoma, 2% undifferentiated carcinoma and 0.7% each of mixed medullary and papillary carcinoma and poorly differentiated carcinoma. Females were predominant 82.4% as compared to males 17.6% with female to male ratio 4.7:1. Maximum number of the patients were seen in 4th decade of life followed by 3rd and 2nd decades., Conclusion: The commonest malignant thyroid lesion was papillary carcinoma. Thyroid cancer was more common in females. Patients of papillary, medullary and follicular carcinomas were found in 3rd and 4th decades of life while poorly and undifferentiated carcinomas were diagnosed from 5th to 7th decades of life.

Objective: To see the expression of cytokeratin 19, a proven helpful marker for the differential diagnosis of neoplastic follicular patterned lesions of thyroid., Methods: This was a retrospective study carried out in the Department of Pathology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi from 2000 to 2005. The haematoxylin and eosin (H&E) stained sections were reviewed and the cases were classified according to already published criteria. On the basis of the recent recommendations by Chemobyl Pathologists Group, encapsulated follicular patterned lesions with questionable nuclear changes were categorized as well - differentiated tumours of uncertain malignant potential (WDT-UMP). Formalin fixed paraffin embedded tissues of follicular adenoma, WDT-UMP and follicular variant of papillary carcinoma were obtained for CK 19 immunostaining., Results: All (16) cases of follicular adenoma were negative for CK19. In a total of 35 cases of WDT- UMP, 10 cases scored 3+ positive for CK19, 15 were 2+ positive and remaining 10 cases were 1+ positive. There were 43 cases of follicular variant of papillary carcinoma with 4+ CK 19 positivity, 14 were 3+ positive and 3 were 2+ positive., Conclusion: CK19 is a good and useful diagnostic marker for differential diagnosis of follicular adenoma, WDT-UMP and follicular variant of papillary carcinoma. The recommendations by Chornobyl Pathologists Group need to be adopted and the cases of WDT-UMP require strict follow-up.

Background and Objectives: To address the need for epidemiologic data on thyroid carcinoma in Pakistan, we evaluated the frequency and types of thyroid carcinoma with respect to age and sex., Methods: In a a retrospective study conducted at the Jinnah Postgraduate Medical Centre in Karachi, we reviewed thyroid lesions reported over a period of 5 years, from July 2000 to June 2005. Pathology slides were studied to determine the types and frequencies of malignant lesions of the thyroid., Results: Of 998 thyroid lesions reviewed, 153 cases were malignant. Papillary carcinoma was the common- est malignant lesion with a frequency of 90.2%, followed by 4.5% for medullary carcinoma, 2% for follicular carcinoma, 2% for undifferentiated carcinoma and 0.7% each for mixed medullary and papillary carcinoma and poorly differentiated carcinoma. Females were predominant (82.4%) as compared with males (17.6%) for a female-to-male ratio 4.7:1. The maximum number of the patients were in the fourth decade of life followed by the third and second decades., Conclusion: The commonest malignant thyroid lesion was papillary carcinoma. Thyroid cancer was more com- mon in females. Papillary, medullary and follicular carcinomas were found in patients in the third and fourth decades of life, while poorly and undifferentiated carcinomas were diagnosed from the fifth to seventh decades of life.