42 results on '"Sunanda Dhar"'
Search Results
2. Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells
- Author
-
Mara Artibani, Kenta Masuda, Zhiyuan Hu, Pascal C. Rauher, Garry Mallett, Nina Wietek, Matteo Morotti, Kay Chong, Mohammad KaramiNejadRanjbar, Christos E. Zois, Sunanda Dhar, Salma El-Sahhar, Leticia Campo, Sarah P. Blagden, Stephen Damato, Pubudu N. Pathiraja, Shibani Nicum, Fergus Gleeson, Alexandros Laios, Abdulkhaliq Alsaadi, Laura Santana Gonzalez, Takeshi Motohara, Ashwag Albukhari, Zhen Lu, Robert C. Bast Jr., Adrian L. Harris, Christer S. Ejsing, Robin W. Klemm, Christopher Yau, Tatjana Sauka-Spengler, and Ahmed Ashour Ahmed
- Subjects
Oncology ,Medicine - Abstract
Similar to tumor-initiating cells (TICs), minimal residual disease (MRD) is capable of reinitiating tumors and causing recurrence. However, the molecular characteristics of solid tumor MRD cells and drivers of their survival have remained elusive. Here we performed dense multiregion transcriptomics analysis of paired biopsies from 17 ovarian cancer patients before and after chemotherapy. We reveal that while MRD cells share important molecular signatures with TICs, they are also characterized by an adipocyte-like gene expression signature and a portion of them had undergone epithelial-mesenchymal transition (EMT). In a cell culture MRD model, MRD-mimic cells showed the same phenotype and were dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings identify EMT and FAO as attractive targets to eradicate MRD in ovarian cancer and make a compelling case for the further testing of FAO inhibitors in treating MRD.
- Published
- 2021
- Full Text
- View/download PDF
3. Author Correction: Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation
- Author
-
Yiyan Zheng, Ritika Sethi, Lingegowda S. Mangala, Charlotte Taylor, Juliet Goldsmith, Ming Wang, Kenta Masuda, Eli M. Carrami, David Mannion, Fabrizio Miranda, Sandra Herrero-Gonzalez, Karin Hellner, Fiona Chen, Abdulkhaliq Alsaadi, Ashwag Albukhari, Donatien Chedom Fotso, Christopher Yau, Dahai Jiang, Sunila Pradeep, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Stefan Knapp, Nathanael S. Gray, Leticia Campo, Kevin A. Myers, Sunanda Dhar, David Ferguson, Robert C. Bast, Anil K. Sood, Frank von Delft, and Ahmed Ashour Ahmed
- Subjects
Science - Published
- 2022
- Full Text
- View/download PDF
4. Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation
- Author
-
Yiyan Zheng, Ritika Sethi, Lingegowda S. Mangala, Charlotte Taylor, Juliet Goldsmith, Ming Wang, Kenta Masuda, Mohammad Karaminejadranjbar, David Mannion, Fabrizio Miranda, Sandra Herrero-Gonzalez, Karin Hellner, Fiona Chen, Abdulkhaliq Alsaadi, Ashwag Albukhari, Donatien Chedom Fotso, Christopher Yau, Dahai Jiang, Sunila Pradeep, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Stefan Knapp, Nathanael S. Gray, Leticia Campo, Kevin A. Myers, Sunanda Dhar, David Ferguson, Robert C. Bast, Anil K. Sood, Frank von Delft, and Ahmed Ashour Ahmed
- Subjects
Science - Abstract
Some anticancer drugs target cell microtubules inhibiting mitosis and cell division. Here, the authors show that CRMP2 induces microtubule bundling and that this activity is regulated by the FER kinase, thus providing a rationale for targeting FER in combination with microtubule-targeting drugs.
- Published
- 2018
- Full Text
- View/download PDF
5. Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies
- Author
-
Karin Hellner, Fabrizio Miranda, Donatien Fotso Chedom, Sandra Herrero-Gonzalez, Daniel M. Hayden, Rick Tearle, Mara Artibani, Mohammad KaramiNejadRanjbar, Ruth Williams, Kezia Gaitskell, Samar Elorbany, Ruoyan Xu, Alex Laios, Petronela Buiga, Karim Ahmed, Sunanda Dhar, Rebecca Yu Zhang, Leticia Campo, Kevin A. Myers, María Lozano, María Ruiz-Miró, Sónia Gatius, Alba Mota, Gema Moreno-Bueno, Xavier Matias-Guiu, Javier Benítez, Lorna Witty, Gil McVean, Simon Leedham, Ian Tomlinson, Radoje Drmanac, Jean-Baptiste Cazier, Robert Klein, Kevin Dunne, Robert C. Bast Jr, Stephen H. Kennedy, Bassim Hassan, Stefano Lise, María José Garcia, Brock A. Peters, Christopher Yau, Tatjana Sauka-Spengler, and Ahmed Ashour Ahmed
- Subjects
Ovarian cancer ,Fallopian tube ,BRCA mutations ,SOX2 ,Screening ,Precancer ,Medicine ,Medicine (General) ,R5-920 - Abstract
Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). The functional and clinical significance of the identified mutations was examined using a combination of population-based whole genome sequencing, targeted deep sequencing, multi-center analysis of protein expression, loss of function experiments in an in-vivo reporter assay and mammalian models, and gain of function experiments in primary cultured fallopian tube epithelial (FTE) cells. We identified frequent mutations involving a 40 kb distal repressor region for the key stem cell differentiation gene SOX2. In the apparently normal FTE, the region was also mutated. This was associated with a profound increase in SOX2 expression (p
- Published
- 2016
- Full Text
- View/download PDF
6. Data from The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers
- Author
-
Ahmed Ahmed, Christina Fotopoulou, Eric O. Aboagye, Ashwag Albukhari, Joanna Hester, Christopher Yau, Sarah P. Blagden, Sunanda Dhar, Stephen Damato, Nina Wietek, Abdulkhaliq Alsaadi, Laura Santana Gonzalez, Jennifer Ploski, Katherine Nixon, Mara Artibani, Leticia Campo, Oloruntoba I. Osagie, Haonan Lu, Zhe Zhong, Paula Cunnea, and Zhiyuan Hu
- Abstract
Purpose:Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier.Experimental Design:We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs.Results:We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition–high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors.Conclusions:The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.
- Published
- 2023
- Full Text
- View/download PDF
7. Table S2 from The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers
- Author
-
Ahmed Ahmed, Christina Fotopoulou, Eric O. Aboagye, Ashwag Albukhari, Joanna Hester, Christopher Yau, Sarah P. Blagden, Sunanda Dhar, Stephen Damato, Nina Wietek, Abdulkhaliq Alsaadi, Laura Santana Gonzalez, Jennifer Ploski, Katherine Nixon, Mara Artibani, Leticia Campo, Oloruntoba I. Osagie, Haonan Lu, Zhe Zhong, Paula Cunnea, and Zhiyuan Hu
- Abstract
Table S2. The QuPath classification results for the immunohistochemistry of CAPS in SOC tissue microarrays.
- Published
- 2023
- Full Text
- View/download PDF
8. The oxford classic links epithelial-to-mesenchymal transition to immunosuppression in poor prognosis ovarian cancers
- Author
-
Abdulkhaliq Alsaadi, Christina Fotopoulou, Eric O. Aboagye, Jennifer Ploski, Mara Artibani, Paula Cunnea, Sarah P. Blagden, Ashwag Albukhari, Oloruntoba I. Osagie, Sunanda Dhar, Joanna Hester, Leticia Campo, Laura Santana Gonzalez, Katherine Nixon, Zhiyuan Hu, Christopher Yau, Haonan Lu, Nina Wietek, Ahmed Ashour Ahmed, Stephen Damato, Zhe Zhong, Imperial College Healthcare NHS Trust- BRC Funding, and Medical Microbiology and Infection Prevention
- Subjects
Adult ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,Adolescent ,medicine.medical_treatment ,Ovary ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Carcinoma ,Humans ,1112 Oncology and Carcinogenesis ,Oncology & Carcinogenesis ,Prospective Studies ,Epithelial–mesenchymal transition ,Aged ,Aged, 80 and over ,Immunosuppression Therapy ,Ovarian Neoplasms ,Chemotherapy ,business.industry ,Maximal Debulking ,Immunosuppression ,Cytoreduction Surgical Procedures ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Cystadenocarcinoma, Serous ,Serous fluid ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,business ,Follow-Up Studies ,Fallopian tube - Abstract
Purpose: Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. Experimental Design: We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs. Results: We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition–high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors. Conclusions: The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.
- Published
- 2021
- Full Text
- View/download PDF
9. Ten-Step Surgical Approach to Management of Pathology of the Ischiorectal Fossa-A Review of the Literature and Application in a Rare Pelvic Schwannoma
- Author
-
Sarah Louise Smyth, Sunanda Dhar, Miss Lucy Cogswell, and Hooman Soleymani majd
- Subjects
Quality of Life ,Rectum ,Humans ,Surgery ,Neurilemmoma - Published
- 2021
10. EPV075/#455 Intraoperative lymph node frozen section examination (FSE) in early stage cervical cancer – a risk stratification algorithm
- Author
-
Nahid Ghanbarzadeh, Zoe Traill, N Sadeghi, Ciro Pinelli, E Jackson, Sunanda Dhar, C Pappa, H Jiang, S Smyth, M Alazzam, and H Soleymani Majd
- Subjects
Cervical cancer ,Frozen section procedure ,medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,Risk stratification ,Medicine ,Radiology ,Stage (cooking) ,business ,medicine.disease ,Lymph node - Published
- 2021
- Full Text
- View/download PDF
11. EPV260/#451 Schwannoma of the pudendal nerve – anatomical considerations in the approach to surgical management of this rare pathology
- Author
-
S Smyth, L Cogswell, Sunanda Dhar, and H Soleymani Majd
- Subjects
medicine.medical_specialty ,business.industry ,Pudendal nerve ,medicine ,Radiology ,Schwannoma ,medicine.disease ,business - Published
- 2021
- Full Text
- View/download PDF
12. Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor initiating cells
- Author
-
P N Pathiraja, Nina Wietek, Robin W. Klemm, Matteo Morotti, Kay Chong, Christer S. Ejsing, S Nicum, Fergus V. Gleeson, Christos E. Zois, Zhimin Lu, Robert C. Bast, Kenta Masuda, Stephen Damato, P C Rauher, Christopher Yau, Alexandros Laios, Zhiyuan Hu, Abdulkhaliq Alsaadi, Garry Mallett, L Santana Gonzalez, Takeshi Motohara, Salma El-Sahhar, Leticia Campo, Sunanda Dhar, Adrian L. Harris, Mohammad KaramiNejadRanjbar, Ahmed Ashour Ahmed, Ashwag Albukhari, Sarah P. Blagden, Tatjana Sauka-Spengler, and Mara Artibani
- Subjects
0301 basic medicine ,Epithelial-Mesenchymal Transition ,Neoplasm, Residual ,Paclitaxel ,medicine.medical_treatment ,Obstetrics/gynecology ,Carcinoma, Ovarian Epithelial ,Carboplatin ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Gene expression ,Adipocytes ,medicine ,Humans ,Cytotoxicity ,Aged ,Aged, 80 and over ,Ovarian Neoplasms ,Chemotherapy ,business.industry ,Fatty Acids ,Cytoreduction Surgical Procedures ,General Medicine ,Middle Aged ,medicine.disease ,Phenotype ,Minimal residual disease ,Neoadjuvant Therapy ,body regions ,030104 developmental biology ,Oncology ,Cell culture ,Fatty acid oxidation ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Cancer research ,Female ,Ovarian cancer ,business ,Oxidation-Reduction ,Research Article - Abstract
Similar to tumor-initiating cells (TICs), minimal residual disease (MRD) is capable of reinitiating tumors and causing recurrence. However, the molecular characteristics of solid tumor MRD cells and drivers of their survival have remained elusive. Here we performed dense multiregion transcriptomics analysis of paired biopsies from 17 ovarian cancer patients before and after chemotherapy. We reveal that while MRD cells share important molecular signatures with TICs, they are also characterized by an adipocyte-like gene expression signature and a portion of them had undergone epithelial-mesenchymal transition (EMT). In a cell culture MRD model, MRD-mimic cells showed the same phenotype and were dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings identify EMT and FAO as attractive targets to eradicate MRD in ovarian cancer and make a compelling case for the further testing of FAO inhibitors in treating MRD.
- Published
- 2021
- Full Text
- View/download PDF
13. 352 Intra-operative frozen section examination of pelvic lymph nodes in early cervical cancer
- Author
-
E Jackson, Susan Addley, Sunanda Dhar, M Alazzam, and H Soleymani Majd
- Subjects
Cervical cancer ,medicine.medical_specialty ,Frozen section procedure ,Intra operative ,business.industry ,Histology ,medicine.disease ,Pelvic lymph nodes ,medicine.anatomical_structure ,medicine ,Radiology ,Lymph ,Stage (cooking) ,business ,Lymph node - Abstract
Introduction Frozen section examination (FSE) of pelvic lymph nodes in early stage cervical cancer is designed to avoid the morbidity of dual therapy. It is however timely and expensive. Method All patients undergoing surgery for early stage cervical cancer between 2010–2019 in a UK tertiary centre were identified (n=180). All patients had pre-operative MRI scans performed and all patients underwent planned intra-operative FSE. Nodes retrieved by FSE were examined by expert pathologists. Patient MRI and histology findings were analysed to suggest an optimal approach to employing FSE. Results 4913 lymph nodes in total were retrieved. 22/180 patients had positive nodes on FSE. 18 of these had intermediate/high grade tumours; and 13 had no suspicious lymph nodes identified on pre-operative MRI. The sensitivity of MRI to detect positive nodes was 40% (95% CI 20% to 63%); specificity 83% (95% CI 76% to 88%); NPV 91% (95% CI 88% to 94%); and PPV 25% (95% CI 16% to 39%). Conclusions Pre-operative MRI did not reliably predict the presence of lymph node involvement in women with intermediate/high grade cervical cancer. Perhaps FSE could be targeted to this group, employing this timely and expensive technique in those at greatest risk having nodal disease.
- Published
- 2020
- Full Text
- View/download PDF
14. 47 An audit of the completeness of the pathological request form for the diagnosis of possible ovarian malignancy in UK tertiary cancer centre
- Author
-
H Soleymani Majd, Susan Addley, Sunanda Dhar, M Daas, and M Alazzam
- Subjects
medicine.medical_specialty ,business.industry ,General surgery ,Retrospective cohort study ,Audit ,Debulking ,medicine.disease ,Radiological weapon ,medicine ,Hormonal therapy ,Family history ,Ovarian cancer ,business ,Pathological - Abstract
Introduction Ovarian cancer prognosis and treatment plan are affected by the accuracy of the pathological report which highly depends on the clinical data. In this Audit, we reviewed the BGCS and The Royal College of Pathology guidelines for reporting ovarian carcinomas recommendation regarding the clinical information required on the pathological request and compare it with the current practice. This audit aims to enhance the pathological request-form of possible ovarian malignancy and increase the adherence of surgeons to the current guidelines. Methods A retrospective study of consecutive 115 pathological request forms for patients who had undergone debulking surgeries for suspected ovarian malignancy at a tertiary university UK hospital. Pathology records were obtained from the 1st January 2016 until 31st December 2018. Results 100% of the request forms contained the demographics, site of tumour origin and marked multiple specimens. However, there was no documentation for the clinical presentation, family history of cancers and history of previous hormonal therapy. Implications Using generic pathology request forms resulted in missing key information which could very helpful to the pathologist in order to provide an accurate diagnosis. Electronic organ-specific pathology forms with dynamic fields must be incorporated into clinical practice for accurate diagnosis and staging. Key information such as clinical presentation, results of previous biopsies, radiological staging if available, and surgery details. Furthermore, add checkboxes for family history of cancers, history of taking any chemotherapy or hormonal replacement therapy.
- Published
- 2020
- Full Text
- View/download PDF
15. 448 Struma ovarii: a rare ovarian malignancy masquerading as a dermoid cyst. A case report
- Author
-
R Mihai, Sunanda Dhar, M Alazzam, Susan Addley, and H Soleymani Majd
- Subjects
medicine.medical_specialty ,endocrine system diseases ,Struma ovarii ,business.industry ,medicine.medical_treatment ,Thyroid ,Thyroidectomy ,Malignant Struma Ovarii ,medicine.disease ,Thyroid carcinoma ,medicine.anatomical_structure ,Dermoid cyst ,medicine ,Histopathology ,Radiology ,Stage (cooking) ,business - Abstract
Introduction Struma ovarii (SO) is rare, accounting for 0.3–1% of ovarian tumours. So is defined histologically as replacement of at least 50% of the ovarian tissue by thyroid tissue. Malignant transformation occurs in less than 5% of cases, most often into a papillary thyroid carcinoma (PTC). An association with a synchronous cancer of the thyroid gland proper exists. Methods We present a case of malignant struma ovarii - considering presentation, diagnosis, management and follow-up. Results A 75 year-old presented with the incidental finding of an ovarian mass on imaging. Pre-operative CA125 was 38 and CT described a 9 cm dermoid cyst. The patient underwent TAH, BSO and omentectomy. Final histopathology reported struma ovarii with co-existing papillary thyroid carcinoma. Post-operative CT confirmed FIGO stage 1A disease. Adjuvant thyroidectomy and radio-active iodine ablation (RAI) therapy were recommended by the multi-disciplinary team (MDT). The patient remained under follow-up, incorporating long-term thyroid-stimulating hormone (TSH) suppression and surveillance of serum thyroglobulin – with no recurrence to date. Conclusions Patients with malignant SO usually present with non-specific symptoms and early stage disease. Very few cases are identified pre-operatively due lack of characteristic features on imaging, with the most common mis-diagnosis being that of a dermoid cyst. CA 125 has no role. Fertility-sparing surgery, pelvic clearance, thyroidectomy and radio-active iodine ablation therapy have all been described in the management of malignant struma ovarii.
- Published
- 2020
- Full Text
- View/download PDF
16. Malignant struma ovarii: surgical, histopathological and survival outcomes for thyroid-type carcinoma of struma ovarii with recommendations for standardising multi-modal management. A retrospective case series sharing the experience of a single institution over 10 years
- Author
-
Radu Mihai, M Alazzam, Hooman Soleymani Majd, Sunanda Dhar, and Susan Addley
- Subjects
Adult ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Malignancy ,Thyroid carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma ,Medicine ,Humans ,Radical surgery ,Aged ,Retrospective Studies ,Ovarian Neoplasms ,030219 obstetrics & reproductive medicine ,Struma ovarii ,business.industry ,General surgery ,Thyroidectomy ,Obstetrics and Gynecology ,General Medicine ,Malignant Struma Ovarii ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Struma Ovarii ,030220 oncology & carcinogenesis ,Female ,business ,Ovarian cancer - Abstract
Struma ovarii is rare, accounting for 0.3–1% of ovarian tumours. Malignant transformation may occur, most often into papillary thyroid carcinoma. There is a paucity of data pertaining to malignant struma ovarii. This paper shares a decade of experience of a single institution in the management of this rare ovarian cancer, exploring the characteristics of this tumour and suggesting a standardised approach to treatment and follow-up. All patients treated for malignant struma ovarii within a large cancer centre over one decade were identified and data collected retrospectively on presentation, diagnosis, management, follow-up and survival outcomes. A literature review was also undertaken. Eleven cases of malignant struma ovarii were managed in the Oxford Cancer Centre between 2010 and 2019, 6 of which were of papillary thyroid carcinoma sub-type. No cases were correctly diagnosed pre-operatively. All patients had stage I disease and were managed surgically—but with variation in radicality. Patients identified as high-risk based on final histopathology underwent additional thyroidectomy and radio-active iodine ablation therapy. One case of synchronous malignancy of the thyroid gland proper was identified. No disease recurrence occurred. Malignant struma ovarii present a diagnostic challenge. Multi-disciplinary team (MDT) input is essential. Unilateral salpingo-oophrectomy may be adequate if stage I; reserving more radical surgery for advanced disease. Histopathological risk-stratification should be used to identify those most likely to benefit from adjuvant thyroid-targeting therapies. Patients require follow-up, anticipating an overall good prognosis.
- Published
- 2020
17. Infections in the gynaecological tract
- Author
-
Sunanda Dhar and Sanjiv Manek
- Subjects
medicine.medical_specialty ,Histology ,Cervical screening ,business.industry ,Context (language use) ,Cervical cytology ,Dermatology ,Tumor formation ,Pathology and Forensic Medicine ,Surgery ,Genital tract ,Cytology ,Pelvic inflammatory disease ,Medicine ,business ,Pathological - Abstract
In the context of infections in the body, those that occur in the gynaecological tract are less common and perhaps less clinically significant compared with other body sites. However, a few infections are important in view of their association with pathological sequelae such as tumour formation or pelvic inflammatory disease complex. This review will discuss some of the most relevant infections, first under histology, which will be further subdivided into locations in the genital tract and then under cytology, which focuses mainly on the infections seen in cervical cytology samples. There will be only brief mention of the less common infections or those that do not produce diagnostic challenges or lead to significant complications.
- Published
- 2017
- Full Text
- View/download PDF
18. The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells
- Author
-
Abdulkhaliq Alsaadi, Garry Mallett, Yun Feng, Matteo Morotti, Mara Artibani, Tingyan Shi, Salma El-Sahhar, Nina Wietek, Zhiyuan Hu, Leticia Campo, Christopher Yau, Tatjana Sauka-Spengler, Yiyan Zheng, Kenta Masuda, Stephen Damato, Kay Chong, Zhe Zhong, Mohammad KaramiNejadRanjbar, Vincenzo Cerundolo, Sunanda Dhar, Stephanie Jones, Vikram Singh Rai, Ahmed Ashour Ahmed, Riccardo Garruto Campanile, Laura Santana Gonzalez, Hooman Soleymani Majd, and David Maldonado-Perez
- Subjects
0301 basic medicine ,Cancer Research ,Cell ,Biology ,Epithelium ,single-cell RNA sequencing ,Transcriptome ,Genetic Heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Fallopian Tube Neoplasms ,Humans ,Fallopian Tubes ,Ovarian Neoplasms ,fallopian tube ,Genetic heterogeneity ,Cancer ,Epithelial Cells ,Cell Biology ,medicine.disease ,Cystadenocarcinoma, Serous ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,ovarian cancer ,Single cell sequencing ,Oncology ,non-genetic heterogeneity ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Female ,Ovarian cancer ,Fallopian tube - Abstract
The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of ∼6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of ∼1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC. Using single-cell RNA sequencing, Hu et al. identify six subtypes of fallopian tube epithelium (FTE) cells in normal human fallopian tube tissues. The FTE cellular subtypes reveal intra-tumoral heterogeneity in serous ovarian cancer (SOC) and define SOC subtypes that correlate with patient prognosis.
- Published
- 2020
- Full Text
- View/download PDF
19. The repertoire of serous ovarian cancer non-genetic heterogeneity revealed by single-cell sequencing of normal fallopian tube epithelial cells
- Author
-
Matteo Morotti, Hooman Soleymani Majd, Kay Chong, Mara Artibani, Zhiyuan Hu, Mohammad KaramiNejadRanjbar, Stephen Damato, Ahmed Ashour Ahmed, Yiyan Zheng, Nina Wietek, Sunanda Dhar, Riccardo Garruto Campanile, Kenta Masuda, Christopher Yau, Tingyan Shi, Abdulkhaliq Alsaadi, Garry Mallett, Laura Santana Gonzalez, Vincenzo Cerundolo, Salma El-Sahhar, and Tatjana Sauka-Spengler
- Subjects
Transcriptome ,Serous fluid ,medicine.anatomical_structure ,Single cell sequencing ,Genetic heterogeneity ,Cancer cell ,Cell ,Serous ovarian cancer ,medicine ,Cancer research ,Biology ,Fallopian tube - Abstract
SummaryThe inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH can be accurately measured when informed by the molecular signatures of the normal cells of origin. We surveyed the transcriptomes of ∼ 4000 normal fallopian tube epithelial (FTE) cells, the cells of origin of serous ovarian cancer (SOC), and identified six FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH that was previously unrecognized. Importantly, NGH-based stratification of ∼1700 tumors robustly predicted survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.HighlightsThe projection of FTE subtypes refines the molecular classification of serous OCComprehensive single-cell profiling of FTE cells identifies 6 molecular subtypesSubstantial non-genetic heterogeneity of HGSOC identified in 1700 tumorsA mesenchymal-high HGSOC subtype is robustly correlated with poor prognosis
- Published
- 2019
- Full Text
- View/download PDF
20. Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation
- Author
-
Lingegowda S. Mangala, Karin Hellner, R. Sethi, David J. P. Ferguson, Mohammad KaramiNejadRanjbar, Ashwag Albukhari, Kevin A. Myers, Stefan Knapp, Gabriel Lopez-Berestein, Dahai Jiang, Juliet Goldsmith, Kenta Masuda, Robert C. Bast, Frank von Delft, Cristian Rodriguez-Aguayo, Christopher Yau, Charlotte Taylor, Leticia Campo, Abdulkhaliq Alsaadi, Fabrizio Miranda, Sunanda Dhar, Sunila Pradeep, Nathanael S. Gray, Ming Wang, Yiyan Zheng, David Mannion, Fiona Chen, Sandra Herrero-Gonzalez, Donatien Chedom Fotso, Ahmed Ashour Ahmed, and Anil K. Sood
- Subjects
0301 basic medicine ,Paclitaxel ,Science ,General Physics and Astronomy ,Mice, Nude ,Nerve Tissue Proteins ,Molecular Dynamics Simulation ,Microtubules ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Microtubule ,In vivo ,Cell Line, Tumor ,Animals ,Humans ,Molecular Targeted Therapy ,Phosphorylation ,RNA, Small Interfering ,lcsh:Science ,Cytotoxicity ,Ovarian Neoplasms ,Multidisciplinary ,Microscopy, Confocal ,Chemistry ,RNA ,General Chemistry ,Protein-Tyrosine Kinases ,Tubulin Modulators ,3. Good health ,Cell biology ,030104 developmental biology ,RNAi Therapeutics ,Microscopy, Fluorescence ,Cell culture ,Intercellular Signaling Peptides and Proteins ,lcsh:Q ,Female ,Collapsin response mediator protein family ,Protein Multimerization ,Neoplasm Transplantation - Abstract
Though used widely in cancer therapy, paclitaxel only elicits a response in a fraction of patients. A strong determinant of paclitaxel tumor response is the state of microtubule dynamic instability. However, whether the manipulation of this physiological process can be controlled to enhance paclitaxel response has not been tested. Here, we show a previously unrecognized role of the microtubule-associated protein CRMP2 in inducing microtubule bundling through its carboxy terminus. This activity is significantly decreased when the FER tyrosine kinase phosphorylates CRMP2 at Y479 and Y499. The crystal structures of wild-type CRMP2 and CRMP2-Y479E reveal how mimicking phosphorylation prevents tetramerization of CRMP2. Depletion of FER or reducing its catalytic activity using sub-therapeutic doses of inhibitors increases paclitaxel-induced microtubule stability and cytotoxicity in ovarian cancer cells and in vivo. This work provides a rationale for inhibiting FER-mediated CRMP2 phosphorylation to enhance paclitaxel on-target activity for cancer therapy., Some anticancer drugs target cell microtubules inhibiting mitosis and cell division. Here, the authors show that CRMP2 induces microtubule bundling and that this activity is regulated by the FER kinase, thus providing a rationale for targeting FER in combination with microtubule-targeting drugs.
- Published
- 2018
21. Surgical upstaging versus provisional clinical stage by computed tomography in type II endometrial cancer: A retrospective study
- Author
-
Roberto Tozzi, Sanjiv Manek, Sunanda Dhar, Yael Hants, Gaetano Valenti, Riccardo Garruto-Campanile, and Raffaella Giannice
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Endometrial cancer ,Medicine ,Computed tomography ,Retrospective cohort study ,Radiology ,Stage (cooking) ,business ,medicine.disease - Published
- 2018
- Full Text
- View/download PDF
22. Toward operative in vivo fluorescence imaging of the c-Met proto-oncogene for personalization of therapy in ovarian cancer
- Author
-
Leticia Campo, Yong Zheng, Alex Laios, Peter Thomas, Kevin A. Myers, Ahmed Ashour Ahmed, Daniel Klotz, Iain D. C. Tullis, Andrea Henricks, Sunanda Dhar, Muna M. El-Kasti, Tony Ng, Christian M. Becker, Shujuan Liu, Davide Volpi, and Borivoj Vojnovic
- Subjects
Cancer Research ,C-Met ,Oncogene ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,Minimal residual disease ,Targeted therapy ,chemistry.chemical_compound ,Oncology ,chemistry ,In vivo ,Cancer research ,Medicine ,Biomarker (medicine) ,business ,Ovarian cancer - Abstract
BACKGROUND Standard biomarker testing of a single macroscopic disease site is unlikely to be sufficient because of tumor heterogeneity. A focus on examining global biomarker expression or activity, particularly in microscopic residual chemotherapy-resistant disease, is needed for the appropriate selection of targeted therapies. This study was aimed at establishing a technique for the assessment of biomarkers of ovarian cancer peritoneal spread. METHODS An in-house developed fluorescent imaging device was used to detect the expression of the c-Met oncogene in ovarian cancer. A modified cyanine 5–tagged peptide, GE137, with a high in vitro affinity for the human c-Met protein, was tested in a panel of ovarian cancer cell lines. Finally, the feasibility of detecting submillimeter ovarian cancer cell peritoneal metastases in vivo was tested through the intravenous injection of GE137 into mice with tumor xenografts. RESULTS Using optical imaging it was possible to detect c-Met expression in submillimeter peritoneal metastases that were freshly excised from a human high-grade serous ovarian cancer. GE137 selectively bound to the c-Met tyrosine kinase without activating survival signaling pathways (AKT or extracellular signal-regulated kinase phosphorylation) downstream of c-Met. GE137 specifically accumulated in SKOv3 ovarian cancer cells expressing c-Met via clathrin-mediated endocytosis and emitted a fluorescent signal that lasted for at least 8 hours in tumor xenografts in vivo with a sustained high signal-to-noise ratio. CONCLUSIONS Our results suggest that intraoperative optical imaging could provide a new paradigm for selecting cancer patients for appropriate targeted therapies, particularly after initial chemotherapy. Cancer 2015;121:202–13. © 2014 American Cancer Society.
- Published
- 2014
- Full Text
- View/download PDF
23. Abstract 5373: The Oxford Ovarian Cancer Predict Chemotherapy Response (OXO-PCR) study: Understanding the genomic drivers of primary chemotherapy-resistant microscopic residual disease
- Author
-
Artibani, Mara, primary, Mallett, Garry, additional, Sunanda, Dhar, additional, KaramiNejadRanjbar, Mohammad, additional, Morotti, Matteo, additional, ElSahhar, Salma, additional, Sauka-Spengler, Tatjana, additional, and Ahmed, Ahmed A., additional
- Published
- 2018
- Full Text
- View/download PDF
24. Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients:Discovery and validation studies
- Author
-
Sonia Gatius, Petronela Buiga, Robert C. Klein, Ruoyan Xu, Christopher Yau, Samar Elorbany, Jean-Baptiste Cazier, Javier Benitez, Rick Tearle, Alba Mota, Gil McVean, Bassim Hassan, Robert C. Bast, Leticia Campo, María Josefa Mosteiro García, Stefano Lise, Fabrizio Miranda, Maria D. Lozano, Kevin Dunne, Daniel M. Hayden, Mohammad KaramiNejadRanjbar, Brock A. Peters, Alex Laios, Karin Hellner, Lorna Witty, Gema Moreno-Bueno, Xavier Matias-Guiu, Sunanda Dhar, Donatien Fotso Chedom, Stephen Kennedy, Tatjana Sauka-Spengler, Rebecca Yu Zhang, Sandra Herrero-Gonzalez, Simon J. Leedham, Maria Ruiz-Miró, K Gaitskell, Ruth M. Williams, Mara Artibani, Ahmed Ashour Ahmed, Radoje Drmanac, Kevin A. Myers, Ian Tomlinson, Karim Ahmed, Medical Research Council (UK), University of Oxford, National Institute for Health Research (UK), Ministerio de Sanidad y Consumo (España), Wellcome Trust, Instituto de Salud Carlos III, Ovarian Cancer Action (Reino Unido), NIHR - Oxford Biomedical Research Centre (Reino Unido), National Institute for Health Research (Reino Unido), Experimental Cancer Medicine Centres, Medical Research Council (Reino Unido), and Cancer Research UK (Reino Unido)
- Subjects
0301 basic medicine ,Pathology ,Cellular differentiation ,Genes, BRCA2 ,Genes, BRCA1 ,SOX2 ,Gene Expression ,lcsh:Medicine ,ComputingMilieux_LEGALASPECTSOFCOMPUTING ,Regulatory Sequences, Nucleic Acid ,medicine.disease_cause ,Ovarian Neoplasms ,lcsh:R5-920 ,Mutation ,education.field_of_study ,High-Throughput Nucleotide Sequencing ,Cell Differentiation ,General Medicine ,Middle Aged ,3. Good health ,Precancer ,medicine.anatomical_structure ,Neoplastic Stem Cells ,Screening ,Female ,lcsh:Medicine (General) ,Research Paper ,Adult ,Image-Guided Biopsy ,medicine.medical_specialty ,Population ,Antineoplastic Agents ,Biology ,Fallopian tube ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Deep sequencing ,03 medical and health sciences ,Ovarian cancer ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Humans ,education ,Fallopian Tubes ,Aged ,Neoplasm Staging ,SOXB1 Transcription Factors ,lcsh:R ,Cancer ,medicine.disease ,BRCA mutations ,030104 developmental biology ,Drug Resistance, Neoplasm ,Cancer research ,Laparoscopy ,Precancerous Conditions - Abstract
Open Access funded by Medical Research Council. Under a Creative Commons license.-- et al., Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). The functional and clinical significance of the identified mutations was examined using a combination of population-based whole genome sequencing, targeted deep sequencing, multi-center analysis of protein expression, loss of function experiments in an in-vivo reporter assay and mammalian models, and gain of function experiments in primary cultured fallopian tube epithelial (FTE) cells. We identified frequent mutations involving a 40kb distal repressor region for the key stem cell differentiation gene SOX2. In the apparently normal FTE, the region was also mutated. This was associated with a profound increase in SOX2 expression (p, This work is funded by the Medical Research Council (H8RSRS00), Ovarian Cancer Action (HER00070), the Oxford Biomedical Research Centre, the National Institute for Health Research (HJRWAC05) and the Experimental Cancer Medicine Centre. MJG is recipient of a research contract from the Instituto de Salud Carlos III of the Ministerio Español de Sanidad y Consumo (Miguel Servet tipo II Program, CPII 13-00047). C.Y. acknowledges the support of an MRC New Investigator Research Grant (Ref No. MR-L001411-1) and the Wellcome Trust Core Award Grant Number 090532-Z-09-Z.
- Published
- 2016
- Full Text
- View/download PDF
25. Routine Intraoperative Frozen Section Examination to Minimize Bimodal Treatment in Early-Stage Cervical Cancer
- Author
-
Krishnayan Haldar, Pubudu Pathiraja, Zhe Wang, Sean Kehoe, Sunanda Dhar, Alexandros Laios, and Phanedra K. Gubbala
- Subjects
Adult ,medicine.medical_specialty ,Uterine Cervical Neoplasms ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Adjuvant therapy ,Medicine ,Frozen Sections ,Humans ,Stage (cooking) ,Radical Hysterectomy ,Radical surgery ,Aged ,Retrospective Studies ,Cervical cancer ,Aged, 80 and over ,Frozen section procedure ,030219 obstetrics & reproductive medicine ,Intraoperative Care ,business.industry ,Obstetrics and Gynecology ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Surgery ,Oncology ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Female ,Lymph Nodes ,business ,Cohort study - Abstract
ObjectiveIn early-stage cervical cancer, single modality therapy is the main objective, to minimize patient morbidity while offering equivalent cure rates. Intraoperative frozen section examination (FSE) of lymph nodes (LNs) can facilitate this aim, ensuring that radical surgery is avoided in patients requiring adjuvant therapy for metastatic LN involvement. We aimed to evaluate the accuracy of routine intraoperative FSE of pelvic LNs during the surgical staging of early-stage cervical cancers and identify a group at low risk for nodal metastases.MethodsA retrospective cohort study of 94 women aged 23 to 80 years who underwent primary surgery and planned intraoperative FSE of the pelvic LNs at the gynecological cancer center in Oxford was performed. The diagnostic value of FSE and the prediction of metastatic nodal disease were assessed by use of preoperative and intraoperative variables.ResultsA total of 1825 LNs were submitted for FSE. Of 94 women (13.8%), 13 had positive LNs at FSE. Two false-negative cases were reported with micrometastases but no false-positive cases. Frozen section examination as a diagnostic test reached a sensitivity of 86.7% and a specificity of 100%. A regression model including grade I to II and tumor size of less than 20 mm identified a low-risk group for LN involvement.ConclusionsIn light of diverse practice patterns, FSE should be routinely offered to women with early-stage cervical cancer in a 1-step protocol. We equally devised a model to predict those patients at least risk of nodal disease, who may be spared of FSE.
- Published
- 2016
26. STI571 (Imatinib Mesylate) Reduces Bone Marrow Cellularity and Normalizes Morphologic Features Irrespective of Cytogenetic Response
- Author
-
Sunanda Dhar, Federica Boecklin, Michael Zaiac, Eduardo Olavarria, John M. Goldman, Jane F. Apperley, Sally Parker, Andrew Chase, Robert P. Hasserjian, Kristin Henry, and Irvin A. Lampert
- Subjects
Pathology ,medicine.medical_specialty ,Myeloid ,business.industry ,Myeloid leukemia ,Erythroid Hyperplasia ,General Medicine ,medicine.disease ,Philadelphia chromosome ,Leukemia ,Myelogenous ,medicine.anatomical_structure ,Imatinib mesylate ,hemic and lymphatic diseases ,medicine ,Cancer research ,Bone marrow ,business - Abstract
The tyrosine kinase inhibitor STI571 (imatinib mesylate, Gleevec) is an effective treatment for chronic myeloid leukemia (CML). We examined bone marrow samples from 53 patients with CML who were receiving STI571 in 3 multicenter phase 2 trials to assess morphologic changes and cytogenetic response to this drug. In most patients with initially increased blasts, the bone marrow blast count rapidly decreased during STI571 therapy. Reductions in cellularity, the myeloid/erythroid ratio (commonly with relative erythroid hyperplasia), and reticulin fibrosis (if present pretreatment) also were seen in most patients, resulting in an appearance resembling normal marrow in many cases. Eighteen patients (34%) had some degree of cytogenetic response. Surprisingly, these striking morphologic changes occurred irrespective of any cytogenetic response to STI571. Thus, STI571 seems to affect the differentiation of CML cells in vivo, causing even extensively Philadelphia chromosome–positive hematopoiesis to exhibit features resembling normal hematopoiesis.
- Published
- 2002
- Full Text
- View/download PDF
27. Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche
- Author
-
Jonathan M. Elkins, Sunila Pradeep, Anil K. Sood, Nathanael S. Gray, Stefan Knapp, Gabriel Lopez-Berestein, Leticia Campo, Robert C. Bast, Cristian Rodriguez-Aguayo, Fabrizio Miranda, Mohammad KaramiNejadRanjbar, Ashwag Albukhari, Sunanda Dhar, Benedikt M. Kessler, Shujuan Liu, Lingegowda S. Mangala, Serena Bivona, Donatien Fotso Chedom, Clara Redondo, Takeshi Motohara, Roman Fischer, Christopher Yau, Charlotte Taylor, Eidarus Salah, Hideyuki Saya, Hwan Geun Choi, Yiyan Zheng, David Mannion, Ruoyan Xu, Dahai Jiang, Sandra Herrero-Gonzalez, Ahmed Ashour Ahmed, Daniel Klotz, Kamal R. Abdul Azeez, and Kevin A. Myers
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Mice, Nude ,Biology ,AMP-Activated Protein Kinases ,Protein Serine-Threonine Kinases ,Metastasis ,03 medical and health sciences ,Mice ,Phosphatidylinositol 3-Kinases ,Internal medicine ,medicine ,Adipocytes ,Animals ,Humans ,Neoplasm Metastasis ,PI3K/AKT/mTOR pathway ,Ovarian Neoplasms ,Kinase ,Autophosphorylation ,medicine.disease ,Mice, Inbred C57BL ,Oncogene Protein v-akt ,030104 developmental biology ,Endocrinology ,Oncology ,Cancer cell ,Cancer research ,Phosphorylation ,Heterografts ,Female ,Signal transduction ,Ovarian cancer ,Acetyl-CoA Carboxylase ,Signal Transduction - Abstract
The adipocyte-rich microenvironment forms a niche for ovarian cancer metastasis, but the mechanisms driving this process are incompletely understood. Here we show that salt-inducible kinase 2 (SIK2) is overexpressed in adipocyte-rich metastatic deposits compared with ovarian primary lesions. Overexpression of SIK2 in ovarian cancer cells promotes abdominal metastasis while SIK2 depletion prevents metastasis in vivo. Importantly, adipocytes induce calcium-dependent activation and autophosphorylation of SIK2. Activated SIK2 plays a dual role in augmenting AMPK-induced phosphorylation of acetyl-CoA carboxylase and in activating the PI3K/AKT pathway through p85α-S154 phosphorylation. These findings identify SIK2 at the apex of the adipocyte-induced signaling cascades in cancer cells and make a compelling case for targeting SIK2 for therapy in ovarian cancer.
- Published
- 2014
28. Fibrolamellar carcinoma: an unusual clinico-radiological presentation
- Author
-
Sunanda Dhar, Nicola H. Strickland, and Preeti Gupta
- Subjects
Adult ,Radiography, Abdominal ,medicine.medical_specialty ,Pathology ,Carcinoma, Hepatocellular ,Radiography ,Metastasis ,Fatal Outcome ,Abdomen ,Ascites ,Carcinoma ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Peritoneal Neoplasms ,Ultrasonography ,business.industry ,Liver Neoplasms ,General Medicine ,medicine.disease ,Hepatocellular carcinoma ,Radiological weapon ,Female ,Radiology ,medicine.symptom ,Presentation (obstetrics) ,Tomography, X-Ray Computed ,business ,Fibrolamellar Carcinoma - Abstract
We report a case of fibrolamellar carcinoma presenting in a 26-year old female. The patient had gross ascites at presentation. Imaging studies (ultrasonography and computed tomography) strongly suggested extensive intraperitoneal drop metastases.
- Published
- 1999
- Full Text
- View/download PDF
29. Primary and secondary intralymphatic histiocytosis
- Author
-
Ed Rytina, Paul Craig, P.G. Norris, Alistair Robson, Sunanda Dhar, Olivia Espinosa, Victoria Swale, Hiva Fassihi, Fiona Lewis, Galia Tamar Ben-Zvi, Naomi Webber, and Farrah Bakr
- Subjects
Adult ,Male ,Systemic disease ,Pathology ,medicine.medical_specialty ,Dermatology ,medicine ,Humans ,Histiocyte ,Aged ,Lymphatic Vessels ,Retrospective Studies ,Crohn's disease ,medicine.diagnostic_test ,CD68 ,business.industry ,Reactive angioendotheliomatosis ,HLA-DR Antigens ,Macrophage Activation ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Histiocytosis ,Lymphatic system ,Skin biopsy ,Female ,business ,Dilatation, Pathologic - Abstract
Background Intralymphatic histiocytosis (IH) is a rare condition often associated with systemic disease. A benign condition, clinical presentations can vary greatly and its cause is largely unknown. Histologically, there are macrophages within distended lymphatic vessels, although this can be an incidental finding or the primary abnormality. Objective We present a series of 7 cases of IH with and without disease associations, and a review of the literature. We propose IH as either primary (without associated conditions) or secondary (associated with systemic disease). Methods This was a retrospective collection of patients whose skin biopsy specimens revealed intralymphatic collections of histiocytes. We reviewed their clinical presentation, disease associations, and staining of slides with CD68 in all cases, D2-40 in 5 cases, and HLA-DR in 4 cases. Results Clinical features were highly variable, and not all cases were associated with systemic disease. One case had admixed reactive angioendotheliomatosis. All 4 cases stained for HLA-DR showed strong expression by the intralymphatic macrophages. Limitations Retrospective analysis and limited numbers are limitations. Conclusion IH is not always associated with systemic disease although macrophage activation nevertheless implies immune activation.
- Published
- 2013
30. Luminescence and deep‐level characteristics of GaAs/Si with atomic layer epitaxy grown predeposition layers
- Author
-
Utpal Das, Mousumi Mazumdar, and Sunanda Dhar
- Subjects
Materials science ,Photoluminescence ,Silicon ,chemistry ,Superlattice ,Atomic layer epitaxy ,Analytical chemistry ,General Physics and Astronomy ,chemistry.chemical_element ,Metalorganic vapour phase epitaxy ,Chemical vapor deposition ,Luminescence ,Layer (electronics) - Abstract
A relatively simple scheme for the growth of high optical quality GaAs layers on Si substrates by metalorganic chemical vapor deposition (MOCVD) technique is reported. The process is analogous to the conventional two‐step growth procedure where the initial thin nucleating layer growth is done by atomic layer epitaxy (ALE) technique, implemented into the MOCVD reactor itself. The photoluminescence from the layer is increased to about sixfold by replacing the normal predeposition growth by the proposed ALE growth technique. Magnitude of luminescence is comparable to that obtained from layers grown with strained layer superlattice buffers. A number of electron and hole traps are detected in the material by deep‐level transient spectroscopy and photocapacitance experiments. A particular electron trap with an activation energy of 0.76 eV is identified as the main nonradiative center by virtue of the decrease of its density in the same proportion as that of the increase in luminescence intensity. Density of som...
- Published
- 1996
- Full Text
- View/download PDF
31. Primary diagnosis of ameloblastoma by fine-needle aspiration: A report of two cases
- Author
-
Promila Bajaj, Sunanda Dhar, and Monisha Choudhury
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Histology ,Pathology and Forensic Medicine ,Ameloblastoma ,Aspiration biopsy ,medicine ,Humans ,medicine.diagnostic_test ,Adamantinoma ,business.industry ,Biopsy, Needle ,Odontogenic tumor ,General Medicine ,Anatomy ,medicine.disease ,Jaw Neoplasms ,Aspiration cytology ,stomatognathic diseases ,Parotid Region ,Fine-needle aspiration ,Cytopathology ,Female ,business - Abstract
Ameloblastoma is the most common epithelial odontogenic tumor, comprising 1% of tumors and cysts arising in the jaws. We describe two cases of ameloblastoma of the jaw diagnosed by fine-needle aspiration cytology. The patients presented with swelling in the parotid region. Cytological examination of the particulate and sticky bloodstained fluid obtained on aspiration showed tightly packed groups of basaloid cells arranged in nests with rounded edges. Palisading epithelial cells and squamous cells with spherical keratinized bodies were the distinctive cytological features. Histologic examination confirmed the presence of ameloblastoma.
- Published
- 2000
- Full Text
- View/download PDF
32. Atomic layer epitaxial predeposition for GaAs growth on Si
- Author
-
Utpal Das, Sunanda Dhar, and Mousumi Mazumdar
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Photoluminescence ,Materials science ,Physics and Astronomy (miscellaneous) ,Silicon ,business.industry ,Superlattice ,Vapor phase ,nutritional and metabolic diseases ,chemistry.chemical_element ,Epitaxy ,chemistry ,Atomic layer epitaxy ,Optoelectronics ,business ,Layer (electronics) ,Transient spectroscopy - Abstract
We report a two‐step growth process, using an atomic layer epitaxially grown GaAs predeposition layer for the growth of GaAs/Si layers by metalorganic vapor phase epitaxy technique. Photoluminescence and deep‐level transient spectroscopy techniques are used to show that the quality of the grown material is comparable to that grown by a much complicated procedure involving strained layer superlattice buffers introduced between the active GaAs layer and the Si substrate.
- Published
- 1996
- Full Text
- View/download PDF
33. ST1571 (imatinib mesylate) reduces bone marrow cellularity and normalizes morphologic features irrespective of cytogenetic response
- Author
-
Robert P, Hasserjian, Federica, Boecklin, Sally, Parker, Andy, Chase, Sunanda, Dhar, Michael, Zaiac, Eduardo, Olavarria, Irvin, Lampert, Kristin, Henry, Jane F, Apperley, and John M, Goldman
- Subjects
Biopsy ,Antineoplastic Agents ,Cell Count ,Cell Differentiation ,Hematopoietic Stem Cells ,Fibrosis ,Piperazines ,Hematopoiesis ,Necrosis ,Pyrimidines ,Bone Marrow ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Benzamides ,Cytogenetic Analysis ,Imatinib Mesylate ,Humans ,Megakaryocytes - Abstract
The tyrosine kinase inhibitor STI571 (imatinib mesylate, Gleevec) is an effective treatment for chronic myeloid leukemia (CML). We examined bone marrow samples from 53 patients with CML who were receiving STI571 in 3 multicenter phase 2 trials to assess morphologic changes and cytogenetic response to this drug. In most patients with initially increased blasts, the bone marrow blast count rapidly decreased during STI571 therapy. Reductions in cellularity, the myeloid/erythroid ratio (commonly with relative erythroid hyperplasia), and reticulin fibrosis (if present pretreatment) also were seen in most patients, resulting in an appearance resembling normal marrow in many cases. Eighteen patients (34%) had some degree of cytogenetic response. Surprisingly, these striking morphologic changes occurred irrespective of any cytogenetic response to STI571. Thus, STI571 seems to affect the differentiation of CML cells in vivo, causing even extensively Philadelphia chromosome-positive hematopoiesis to exhibitfeatures resembling normal hematopoiesis.
- Published
- 2002
34. Abstract LB-164: Towards operative in vivo fluorescence imaging of c-Met proto-oncogene for personalization of therapy in ovarian cancer
- Author
-
Iain D. C. Tullis, Leticia Campo, Daniel Klotz, Tony Ng, Peter R. Thomas, Alex Laios, Christian M. Becker, Davide Volpi, Shujuan Liu, Yong Zheng, Sunanda Dhar, Kevin A. Myers, Ahmed Ashour Ahmed, Andrea Henricks, Borivoj Vojnovic, and Muna El-Kasti
- Subjects
Cancer Research ,Chemotherapy ,Pathology ,medicine.medical_specialty ,C-Met ,Tumour heterogeneity ,Oncogene ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,chemistry.chemical_compound ,Oncology ,chemistry ,In vivo ,Cancer research ,Medicine ,Biomarker (medicine) ,business ,Ovarian cancer - Abstract
The recent recognition of the scale of the problem of tumour heterogeneity has made it clear that standard biomarker testing of a single macroscopic disease sites is unlikely to be sufficient. A focus on examining global biomarker expression or activity is needed for appropriate selection of targeted therapies. A particular attention to microscopic residual chemotherapy-residual disease (MRCD) would ensure appropriate targeting of chemotherapy resistance. However, the techniques for global assessment of biomarkers in patients with MRCD have not established. Using an in-house developed fluorescent imaging device we show that it is possible to identify global c-Met expression in submillimeter peritoneal metastases that were freshly excised from a human high-grade serous ovarian cancer. We evaluated a modified Cy5-tagged peptide (GE137) that selectively binds to the c-Met tyrosine kinase and demonstrated the feasibility of detecting submillimeter ovarian cancer cell peritoneal metastases in vivo following intravenous injection of this peptide. GE137 specifically accumulated in cells that express c-Met via clathrin-mediated endocytosis and emitted a fluorescent signal that lasted for at least 8 hours in tumour xenografts in vivo with a sustained high signal to noise ratio. Thus, intraoperative optical imaging could provide a new paradigm for selecting cancer patients with MRCD for appropriate targeted therapies following initial chemotherapy. Citation Format: Shujuan Liu, Yong Zheng, Davide Volpi, Muna El-Kasti, Daniel Klotz, Iain Tullis, Andrea Henricks, Leticia Campo, Kevin Myers, Alex Laios, Peter Thomas, Tony Ng, Sunanda Dhar, Christian Becker, Borivoj Vojnovic, Ahmed A. Ahmed. Towards operative in vivo fluorescence imaging of c-Met proto-oncogene for personalization of therapy in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-164. doi:10.1158/1538-7445.AM2014-LB-164
- Published
- 2014
- Full Text
- View/download PDF
35. Recurrent arterial embolization from a metastatic germ cell tumor invading the left atrium
- Author
-
Chandana P. Ratnatunga, Anjana Singh, Maher D. Dahdal, Sunanda Dhar, and David Philip Jenkins
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Malignancy ,Metastasis ,Heart Neoplasms ,Pneumonectomy ,Testicular Neoplasms ,Ischemia ,medicine ,Humans ,Embolization ,Heart Atria ,Leg ,business.industry ,Arterial Embolization ,Endodermal Sinus Tumor ,medicine.disease ,Endodermal sinus tumor ,Neoplastic Cells, Circulating ,Embolism ,Pulmonary Veins ,Surgery ,Metastatic Germ Cell Tumor ,Cardiology and Cardiovascular Medicine ,business ,Pulmonary Embolism - Abstract
Arterial embolization of a malignant tumor is extremely rare. We report an unusual case of a young adult man who presented with acute lower limb ischemia and a mass in the right lung and left atrium. These clinical manifestations were the result of metastases and embolization from a germ cell tumor and were the first indication of malignancy in this patient. The importance of appropriate investigations in the subsequent treatment is stressed.
- Published
- 2001
36. Nature and distribution of electrically active defects in Si‐implanted and lamp‐annealed GaAs
- Author
-
Pallab Bhattacharya, K. S. Seo, and Sunanda Dhar
- Subjects
chemistry.chemical_classification ,Electron mobility ,Photoluminescence ,Materials science ,Silicon ,business.industry ,Annealing (metallurgy) ,Analytical chemistry ,General Physics and Astronomy ,chemistry.chemical_element ,Penning trap ,Ion implantation ,chemistry ,Hall effect ,Optoelectronics ,business ,Inorganic compound - Abstract
The nature and spatial distribution of deep levels arising from defects in device‐quality, Si‐implanted, and lamp‐annealed liquid encapsulated Czochralski GaAs have been investigated. The best activation and mobility values are obtained for annealing times and temperatures of 3–5 s and 900–950 °C, respectively. Further improvements are obtained for a two‐step annealing in which a second step at 840–850 °C for 15–40 s follows the main anneal step. From Hall measurements, average layer mobilities of 4000 cm2/V s and activation of 55–65% are obtained for a Si+ dose of 6.5×1012 cm−2 at 100 keV. Electrically active deep‐level traps were studied by sensitive deep‐level transient spectroscopy (DLTS) and optical DLTS techniques. A dominant 0.57‐eV electron trap, which is also present in furnace‐annealed GaAs, originates from implantation damage and is possibly related to VGa. Additional electron traps with activation energies of 0.35 and 0.40 eV are present only in lamp‐annealed GaAs. Commonly observed hole traps...
- Published
- 1985
- Full Text
- View/download PDF
37. Deep levels in as‐grown and Si‐implanted In0.2Ga0.8As–GaAs strained‐layer superlattice optical guiding structures
- Author
-
Sunanda Dhar, Pallab Bhattacharya, and Utpal Das
- Subjects
Materials science ,Silicon ,Superlattice ,Analytical chemistry ,General Physics and Astronomy ,Thermal ionization ,chemistry.chemical_element ,Heterojunction ,Electron ,Penning trap ,Molecular physics ,Ion implantation ,chemistry ,Ionization - Abstract
Trap levels in about 2-micron In(0.2)Ga(0.8)As(94 A)/GaAs(25 A) strained-layer superlattices, suitable for optical waveguides, have been identified and characterized by deep-level transient spectroscopy and optical deep-level transient spectroscopy measurements. Several dominant electron and hole traps with concentrations of approximately 10 to the 14th/cu cm, and thermal ionization energies Delta-E(T) varying from 0.20 to 0.75 eV have been detected. Except for a 0.20-eV electron trap, which might be present in the In(0.2)Ga(0.8)As well regions, all the other traps have characteristics similar to those identified in molecular-beam epitaxial GaAs. Of these, a 0.42-eV hole trap is believed to originate from Cu impurities, and the others are probably related to native defects. Upon Si implantation and halogen lamp annealing, new deep centers are created. These are electron traps with Delta-E(T) = 0.81 eV and hole traps with Delta-E(T) = 0.46 eV. Traps occurring at room temperature may present limitations for optical devices.
- Published
- 1986
- Full Text
- View/download PDF
38. Material properties and optical guiding in InGaAs-GaAs strained layer superlattices—a brief review
- Author
-
Utpal Das, Yasunobu Nashimoto, Sunanda Dhar, F. Y. Juang, and Pallab Bhattacharya
- Subjects
Materials science ,Ingaas gaas ,business.industry ,Band gap ,Superlattice ,Condensed Matter Physics ,Epitaxy ,Electronic, Optical and Magnetic Materials ,Characterization (materials science) ,Condensed Matter::Materials Science ,Optics ,Materials Chemistry ,Optoelectronics ,Electrical and Electronic Engineering ,business ,Material properties ,Layer (electronics) ,Refractive index - Abstract
Due to the absence of lattice-matching requirements, strained-layer superlattices offer a large tunability in bandgap and other material properties suitable for device applications. Encouraging progress has been made in the molecular-beam epitaxial and metalorganic-vapor-phase-epitaxial growth of strained-layer superlattices and in their characterization. These have been briefly reviewed here. Since a strained-layer superlattice allows the use of InzGa,_,vAs layers with x-values up to - 1.0, a large variation of the refractive index from that in GaAs occurs due to mismatch strain and alloying. This variation in refractive index has been calculated. The increase in refractive index can be used to form optical guides in the SLS and such guides with good vertical confinement is demonstrated. Preliminary measurements of the impact-ionization parameters and deep-level traps in these materials are also reported. a/@ values close to and slightly greater than unity are measured. A single electron trap with thermal activation energy equal to 0.16 eV is identified.
- Published
- 1986
- Full Text
- View/download PDF
39. Low defect densities in molecular beam epitaxial GaAs achieved by isoelectronic In doping
- Author
-
Paul R. Berger, Feng Yuh Juang, Sunanda Dhar, and Pallab Bhattacharya
- Subjects
chemistry.chemical_classification ,Photoluminescence ,Physics and Astronomy (miscellaneous) ,Condensed matter physics ,chemistry ,Exciton ,Doping ,Electron ,Molecular beam ,Crystallographic defect ,Inorganic compound ,Molecular physics ,Molecular beam epitaxy - Abstract
We have studied the effects of adding small amounts of In (0.2–1.2%) to GaAs grown by molecular beam epitaxy. The density of four electron traps decreases in concentration by an order of magnitude, and the peak intensities of prominent emissions in the excitonic spectra are reduced with increase in In content. Based on the higher surface migration rate of In, compared to Ga, at the growth temperatures it is apparent that the traps and the excitonic transitions are related to point defects. This agrees with earlier observations by F. Briones and D. M. Collins [J. Electron. Mater. 11, 847 (1982)] and B. J. Skromme, S. S. Bose, B. Lee, T. S. Low, T. R. Lepkowski, R‐Y. DeJule, G. E. Stillman, and J. C. M. Hwang [J. Appl. Phys. 58, 4702 (1985)].
- Published
- 1986
- Full Text
- View/download PDF
40. Low‐loss optical waveguides made with molecular beam epitaxial In0.012Ga0.988As and In0.2Ga0.8As‐GaAs superlattices
- Author
-
Sunanda Dhar, Pallab Bhattacharya, and Utpal Das
- Subjects
Optical fiber ,Materials science ,Fabrication ,Physics and Astronomy (miscellaneous) ,business.industry ,Scattering ,Superlattice ,Attenuation ,law.invention ,Optics ,law ,business ,Ternary operation ,Molecular beam ,Molecular beam epitaxy - Abstract
Low-loss optical guiding in In-doped GaAs is demonstrated for the first time. Ridge waveguides are made with single In(0.012)Ga(0.988)As ternary layers and In(0.2)Ga(0.8)As-GaAs superlattices. Attenuation constants of about 1.3 dB/cm are measured and the principal loss mechanism is identified to be scattering at the ridge walls. It is expected that improved fabrication techniques will lead to guides with attenuation less than or equal to 0.5 dB/cm.
- Published
- 1986
- Full Text
- View/download PDF
41. IVA-3 performance characteristics of high-quality GaAs AlxGa1-xAs superlattice avalanche photodiodes
- Author
-
Sunanda Dhar, F. Y. Juang, Yasunobu Nashimoto, and P. K. Bhattacharya
- Subjects
Materials science ,Photoluminescence ,business.industry ,Superlattice ,Avalanche photodiode ,Electronic, Optical and Magnetic Materials ,Photodiode ,law.invention ,Gallium arsenide ,chemistry.chemical_compound ,Quality (physics) ,chemistry ,law ,Optical materials ,Optoelectronics ,Electrical and Electronic Engineering ,business ,Photonic crystal - Published
- 1985
- Full Text
- View/download PDF
42. Investigation of molecular beam epitaxial In0.53Ga0.47As regrown on liquid phase epitaxial In0.53Ga0.47As/InP
- Author
-
P. K. Bhattacharya, Albert Chin, W. P. Hong, Paul R. Berger, Y. Nashimoto, and Sunanda Dhar
- Subjects
Deep-level transient spectroscopy ,Materials science ,Photoluminescence ,Hall effect ,General Engineering ,Analytical chemistry ,Recrystallization (metallurgy) ,Epitaxy ,Molecular beam ,Surface reconstruction ,Molecular beam epitaxy - Abstract
Molecular beam epitaxial In0.53Ga0.47As regrown on high‐purity liquid phase epitaxial In0.53Ga0.47As has been investigated. The regrown layers have been characterized by Hall measurements, low‐temperature photoluminescence, and deep level transient spectroscopy. The regrown layers have properties comparable to material directly grown on InP substrates.
- Published
- 1986
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.