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Home > Expression of Mismatch Repair Proteins in Colorectal Cancer at Aga Khan University Hospital, Nairobi

Expression of Mismatch Repair Proteins in Colorectal Cancer at Aga Khan University Hospital, Nairobi

Thesis Info

Author

Wahome, Charles M.

Department

Pathology (East Africa)

Program

MMed

Institute

Aga Khan University

Institute Type

Private

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2013

Thesis Completion Status

Completed

Subject

Medicine

Language

English

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676728050866

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Introduction: Microsatellite instability is one of three molecular pathways described in the pathogenesis of colorectal carcinoma. The presence of microsatellite instability in patients with colorectal cancer has implications for prognosis and family counselling. Deficiency in mismatch repair genes leads to microsatellite instability and this can be reliably demonstrated in formalin fixed paraffin embedded tissue by methods, which include immunohistochemistry for the detection of mismatch repair proteins. Local data show a disproportionately large number of younger patients with colorectal cancer compared to that documented in Caucasians. Colorectal cancer in younger ages is often attributed to deficient mismatch repair. The objective of this study therefore, was to determine the proportion of colorectal cancers associated with the microsatellite instability pathway through detection of the mismatch repair proteins on immunohistochemistry. Materials and Methods: This was a retrospective study of 80 colorectal adenocarcinoma resection specimens received over a three-year period from January 2009 to January 2012. The mismatch repair gene mutation expression was analysed by immunohistochemical staining for products of mismatch repair genes. Associated clinical and pathologic characteristics were reviewed and documented. Results: The proportion of deficient mismatch colorectal cancer in the study was 19.4% [95% CI 11.7%-30.4%].There was a significant but weak association between mismatch repair gene protein expression and tumour grade, and tumour infiltrating lymphocytes (tumour grade Cramer’s V=0.263, p=0.031; tumour infiltrating lymphocytes Cramer’s V=0.246, p=0.044). Mismatch repair gene protein expression outcome showed significant but moderately strong association with the anatomic site of tumour, and tumour histological type (anatomic site Cramer’s V=0.469, p=0.001, tumour histological type Cramer’s V=0.469, p=0.001,). Conclusions: The study provides preliminary data of the contribution of the deficient mismatch repair molecular pathway of colorectal cancer in Kenya.
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صبح قفس کا جمالیاتی پہلو

صبحِ قفس کا جمالیاتی پہلو
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غزلیات پر مشتمل صبح قفس کا آغاز حسب روایت حمدو نعت سے ہوتا ہے۔ شاعر ان اصناف کی نزاکتوں سے کماحقہ آگاہ ہیں۔ وہ حمد و نعت کی گہرائی وگیرائی سے اچھی طرح شناسا ہیں۔ حمد کا ایک شعر الوہیت رب...

Buddhism In Gandhara

The present study entitled “Buddhism in Gandhara” focuses on the religious faith of Gandharans during the Kushan Empire, especially during Kanishka Reign when Buddhism became popular. This research focuses on the religious art works flourished during the regime, including stone sculpture of Gandhara and Mathura reflect the Hellenistic style of Gandharan Buddhist art. It also deals with the artifacts, coins, inscriptions, narrative sculptures from Kushan to ascertain Gandharan Buddhist tradition as documented in art, archaeology, and epigraphy, which comes mainly from the region. The Study can be distinguished as a special case study of its own nature for being conducted in the geographical boundaries, where Kushan and Gandhara art was experimented and practiced which afterwards achieved a status of the full-scale culture of the area. The main aim of the research was to study the religious aspects of the inhabitants of the Kushan period, which was prominent in the living patterns of different social classes, structural design of the buildings, attires and cultural outfits of various segments of the society as well as personal features like ornaments, headdresses, and social rituals in shaping the cultural contours of Gandhara art. The study, based on empirical data collected from various museums and archaeological sites, particularly from excavated areas around Taxila valley, which reflect a special understanding of religious artwork during the regime of Kushans supporting a close link with the Kings and Princess during their control of South Asian region. This paper concludes that Buddhism was a thriving religion during the Greek regime and was supported by the state.

Morphological and Biochemical Adaptations of Local Cultivars of Barley Hordeum Vulgare L. under Drought

Barley (Hordeum vulgare L.) ranks fifth among important crops worldwide having the annual production of 136 million metric tonnes. In comparison with other cereal crops, it is more tolerant to water shortage, cold environments and salinity and hence is a crop of marginal lands. Drought is an important factor limiting barley yield because about two third of the area of barley production in Pakistan is rainfed. The present study was focused to unravel the morphological and biochemical dynamics and processes underlying adaptation to drought in local genotypes of barley. After initial screening in hydroponics at early growth stage, the barley genotypes were grouped into drought sensitive and tolerant categories using Ward’s hierarchical clustering procedure. The drought sensitive group comprised of nine genotypes (004186, Jau-83, Sanober-96, 004222, Haider-93, 004325, 005130, Soorab-96 and Jau-87) while the tolerant group consisted of six genotypes (004223, 004360, Frontier -87, 004201, 017655 and 005137). Drought linked simple sequence repeat (SSR) primers also separated sensitive and tolerant genotypes into different groups in UPGMA clustering. Among the drought sensitive group, 004186 was found to be the most sensitive genotype and 004223 as the most tolerant one in the tolerant group. Dehydrins are the proteins who play an important role in plant adaptation to drought. Immunoblots were used to characterize dehydrins in local barley genotypes. The maximum dehydrin expression was found in the most drought tolerant genotype 004223 while the most sensitive genotype 004186 lack this expression. Further characterizations of barley genotypes were done in a pot experiment at tillering, booting and milking stages of development. The data recorded was analysed using CRD. The milking stage came out 18 to be the most responsive towards drought. Genetic diversity analysis was done using Inter simple sequence repeat (ISSR) primers. The resultant dendrogram clustered barley cultivars and landraces into two separate groups. Global changes in protein profiles of the most sensitive (004186) and the most tolerant genotype (004223) were further investigated using proteomics technique. After the extraction of proteins from shoots, their separation was carried out by 2D-PAGE and staining was done with coomassie brilliant blue. Among the commom proteins between sensitive and tolerant genotypes in response to drought, the expression of Vacuolar Proton ATPase subunit E was increased while Photosystem I reaction centre II was decreased. Many of the proteins involved in photosynthesis and metabolism were decreased in the sensitive genotype under drought, however, they were increased in the tolerant genotype. Similarly, proteins related to energy, defense and transportation were also increased in the tolerant genotype only. To further investigate the response of three most drought tolerant genotypes (004223, 004360 and Frontier-87), a confirmatory experiment was conducted using proteomics approach. Among these genotypes, the twofold increase in the expression of Alpha SNAP and Methionine synthase alongwith Glycine decarboxylase indicated their crucial role in water stress tolerance. In conclusion, these target proteins involved in maintaining ion balance, chromatin protection and suppression of ROS came out to be the candidates for drought stress acclimation in barley genotypes.