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Biomedical subjects

Ashish Chandra

Publications and source records attributed to Ashish Chandra.

At least 19 recordsLinked to original sources
PubMed2025

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy. We also uncover a co-evolution between the tumor and the T cell repertoire, as well as a longitudinal shift in the TME from an anti-tumor to an immunosuppressive state, linked to the acquisition of recurrently late ccRCC drivers 9p loss and SETD2 mutations. Our study reveals clinically-relevant and hitherto underappreciated non-genetic evolution patterns in ccRCC.

Journal Article↗
PubMed2006

Clinico-pathological aspects of colorectal serrated adenomas.

AIM: To study the association of colorectal serrated adenomas (SAs) with invasive carcinoma, local recurrence, synchronicity and metachronicity of lesions. METHODS: A total of 4,536 polyps from 1,096 patients over an eight-year period (1987-1995) were retrospectively examined. Adenomas showing at least 50% of serrated architecture were called SAs by three reviewing pathologists. RESULTS: Ninety-one (2%) of all polyps were called SAs, which were found in 46 patients. Invasive carcinomas were seen in 3 out of 46 (6.4%) patients, of whom one was a case of familial adenomatous polyposis (FAP). A male preponderance was noted and features of a mild degree of dysplasia were seen in majority (n=75, 83%) of serrated adenomas. Follow-up ranged 1-12 years with a mean time of 5.75 years. Recurrences of SAs were seen in 3 (6.4%) cases, synchronous SAs in 16 (34.8%) cases and metachronous SAs in 9 (19.6%) cases. CONCLUSION: Invasive carcinoma arising in serrated adenoma is rare, accounting for 2 (4.3%) cases studied in this series.

Adenoma↗
PubMed2006

Regulation of E-cadherin expression by VHL and hypoxia-inducible factor.

Mutations in von Hippel-Lindau tumor suppressor gene (VHL) underlie the VHL hereditary cancer syndrome and also occur in most sporadic clear cell renal cell cancers (CCRCC). Currently, the mechanism(s) by which VHL loss of function promotes tumor development in the kidney are not fully elucidated. Here, we show that VHL inactivation in precancerous lesions in kidneys from patients with VHL disease correlates with marked down-regulation of the intercellular adhesion molecule E-cadherin. Moreover, in VHL-defective cell lines (RCC4 and RCC10) derived from sporadic CCRCC, reexpression of VHL was found to restore E-cadherin expression. The product of the VHL gene has multiple reported functions, the best characterized of which is its role as the recognition component of an ubiquitin E3 ligase complex responsible for mediating oxygen-dependent destruction of hypoxia-inducible factor-alpha (HIF-alpha) subunits. We show that HIF activation is necessary and sufficient to suppress E-cadherin in renal cancer cells. Given the fundamental role of E-cadherin in controlling epithelial behavior, our findings give insight into how VHL inactivation/HIF activation may lead to kidney cancer and also indicate a mechanism by which reduced oxygenation could alter E-cadherin expression in other cancers and influence normal homeostasis in other epithelia.

Adult↗
PubMed2006

Cytologic diagnosis of pancreatic endocrine tumors by endoscopic ultrasound-guided fine-needle aspiration: a review.

Precise localization and diagnosis of pancreatic endocrine tumors (PETs) is important, because pancreatic PETs have different clinical and biological behavior and treatment modalities than do exocrine pancreatic tumors. In contrast to the much more common exocrine adenocarcinomas, cytologic studies of PET are relatively rare and many cytopathologists lack experience with the cytomorphologic features of these tumors.During the last 10 yr, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has matured into an accurate, highly sensitive, and cost-effective modality for the preoperative localization of pancreatic PETs. This has resulted in an increased number of PETs first sampled as cytology specimens. This manuscript focuses on the cytomorphologic features most suggestive of pancreatic PETs, differential diagnosis, and diagnostic pitfalls of PETs. The technical development of EUS-guided FNA and the ancillary studies for pancreatic PETs are also reviewed. The data summarized in this review indicate that EUS-FNA is a valuable method in the recognition of pancreatic PETs and in most cases cytopathologists could reach a correct diagnosis of these tumors, including their hormone producing capability on aspirated cytologic material.

Adenocarcinoma, Papillary↗
PubMed2006

Open partial nephrectomy: outcomes from two UK centres.

OBJECTIVE: To define the current achievable outcomes from open partial nephrectomy (OPN) in the UK at a time when other treatments for small kidney tumours are increasingly being advocated. Current knowledge of the effectiveness of OPN is limited by the fact that published data are almost exclusively derived from a very few centres of established world renown. PATIENTS AND METHODS: We retrospectively reviewed 100 consecutive planned OPNs in 90 patients at two UK centres; 93 operations were for suspected cancer. The median (range) tumour size was 3.8 (1.2-9) cm. In all, 42 OPNs were imperative for patients with a single kidney (14), synchronous bilateral tumours (20), or renal impairment alone (eight). In 42 patients with a tumour of < or = 4 cm and a normal contralateral kidney the decision to do OPN was considered elective. There were 10 additional operations in seven patients with Von Hippel-Lindau (VHL) disease. In all, 21 OPNs were in the context of a single kidney. RESULTS: In all, 95 OPNs were successfully completed; one operation was abandoned and there were four nephrectomies, including two for bleeding, one for a positive margin on frozen-section analysis, and one for multifocal tumours. The median warm/cold ischaemia time was 20/33 min. The intraoperative/early complication rate was 36%, including a major complication rate of 11% and re-operation rate for primary bleeding of 3%. Of 36 complications, 30 (83%) were in 23 patients with either an imperative indication or VHL. Complications were more common in the imperative/VHL group (59%) than in the elective/other group (12%). Renal function was preserved in 80 of 100 (80%) OPNs overall. Creatinine levels returned to baseline in 11 of 21 (50%) patients with renal impairment before OPN and in 12 of 20 (60%) with a single kidney, whilst five of 21 (24%) with a single kidney needed dialysis after OPN. The median (range) stay after surgery was 6 (3-50) nights. A malignant diagnosis was confirmed in 76 of 93 (82%) specimens on final histopathology. There were 11 of 100 (11%) positive margins, one managed by immediate conversion to nephrectomy and the remaining 10 managed expectantly. After a median (range) follow-up of 24 (1-69) months there were no deaths from kidney cancer, but three patients had local recurrences and two others had developed metastatic recurrence. CONCLUSION: OPN is complex surgery, especially in the imperative setting, but very good results are achievable outside established centres of world renown. It provides good cancer control in the short term with low renal morbidity. These results may act as a reference point in the UK by which to compare results of new treatments for kidney cancer.

Adolescent↗
PubMed2006

Let's reach all of the market for health administration education: design, development, and delivery issues in distance delivery.

Web-based distance learning is an up and coming form of education. Web-based education delivered via a Web browser through the Internet has been found to be less expensive, more efficient, and sometimes more effective than classroom training. In the distance learning environment, the traditional "lecture and chalkboard" classroom pedagogy is completely absent. The virtual classroom becomes an "active learning" environment in which students, while utilizing technology, are able to discuss health administration concepts, analyze cases, work exercises, and discuss and share these interactively with both the instructor and fellow classmates. This method of Health Administration Education encourages students to learn from each other and promotes the open exchange of ideas and experiences. It does not require working students to put their careers on hold while they continue their studies. In this paper, we explore the opportunities and challenges of delivering web-based Health Administration courses via the Internet. Included is a discussion of the design, development, and delivery of a distance learning, web-based Health Administration Education system.

Adult↗
PubMed2006

Pharmacy layout: What are consumers' perceptions?.

The physical layout of a retail pharmacy can play a significant role in the development of the customers' perceptions which can have a positive (or negative) impact on its sales potential. Compared to most general merchandise stores, pharmacies are more concerned about safety and security issues due to the nature of their products. This paper will discuss these aspects as well as the physical and professional environments of retail pharmacies that influence the perceptions of customers and how these vary whether chain, independent, or hospital pharmacies.

Commerce↗
PubMed2006

What do consumers and healthcare providers in West Virginia think of long-term care?

In recent years, the media has portrayed long-term care in a negative light, with exposè news stories on skilled nursing facilities, personal care homes, and hospitals that provide long-term care. There have been few positive news stories to counter the negative ones, and there is concern that the public perception of long-term care is inaccurate. The authors conducted the following study to evaluate how the West Virginia consumer perceives and defines long-term care and if there is a difference in that perception as compared with healthcare workers' perceptions and definitions of long-term care. The results of the study indicate that the respondents' education level, not occupation, has the most significant influence on respondents' definitions and perceptions of long-term care. Respondents felt that although media articles are informative, they are not accurate, and that long-term care is a needed service they would consider both for themselves and for a loved one. The results of the study suggest that current marketing strategies employed by nursing homes are working, as respondents largely believe that long-term care is provided in nursing homes and that they would likely seek care there if needed.

Adolescent↗
PubMed2006

Overall outpatient satisfaction and its components: perceived changes at the Huntington VA Medical Center over five years.

The number of veterans obtaining healthcare services at Huntington Veteran's Administration Medical Center (HVAMC) had significantly increased over the five-year span from fiscal year 2000 through fiscal year 2004. The authors' purpose in this study was to determine changes in outpatient satisfaction levels at HVAMC over that five-year period. The authors assessed the following specific measures of patient satisfaction: courtesy, access, patient preferences, coordination of care, education and information, emotional support, overall quality, pharmacy services, and overall satisfaction. Of the 17,000 patients meeting the criteria, 630 were randomly selected; 195 patients completed surveys, resulting in a 31% response rate. Results demonstrated an overall significantly higher level of patient satisfaction than five years previously. On the basis of these results, the medical center administration can probably conclude that any process he improvements made over the five-year period have been successful.

Ambulatory Care↗
PubMed2005

A critical examination of team-teaching of health care administration courses: student, faculty, and administration perspective.

There are several teaching techniques adopted by faculty in order to provide information to students in the most effective manner. One of the relatively new teaching techniques is known as team-teaching. It has been observed that over the recent years this form of teaching has been gaining increasing interest and popularity among academicians. Nevertheless, there seems to be a great deal of confusion associated with team-teaching format. This paper attempts to clarify the various definitions and concerns that are associated with this form of teaching. The pros and cons of this form of teaching are discussed in detail.

Administrative Personnel↗
PubMed2004

Laparoscopic nephroureterectomy for adult incontinence caused by functioning ectopic pelvic kidney draining into vagina.

A 29-year-old woman had been continent of the majority of her urine for her entire life but had constant, uncontrollable dribbling. A contrast CT scan showed a solitary functioning left kidney and a dysplastic right pelvic kidney with a tortuous dilated ureter running close to the vaginal vault. The kidney was removed whole at transperitoneal laparoscopy, rendering the patient continent. This is the first such case reported in an adult.

Abnormalities, Multiple↗
PubMed2004

Strategic imperatives for globalization of industries in developing countries: an Indian pharmaceutical industry example.

The annual global pharmaceutical sales have grown over 466 billion dollars, almost 50% of which comes from North America. Among developing countries, India, with 16% of the world population, accounts for only a small percentage of the global pharmaceutical industry. Until recently, India has had virtually no pharmaceutical industry worth the name producing drugs from basic raw materials and it used to rely mostly on the imports from countries like the USA and England for all its requirements of drugs. On the other hand, India has seen a plethora of multinational pharmaceutical companies come and do business in India. This paper develops a matrix which provides a broad guidance to the mid- to large-size Indian pharmaceutical domestic companies, which should embark on the path to global expansion to establish their might as well.

Developing Countries↗