Publications

Abstract

• Racial/Ethnic disparities in thyroid cancer stratified by risk factors (12/2022)
• Differential microRNA expression in thyroid cancer subtypes (12/2022) (link)
• Differential expression of vitamin D binding protein in thyroid cancer health disparities (03/2022) (link)
• Aminoflavon in breast cancer (03/2022) (link)
• Impact of Covid-19 on the pathophysiological changes on fetomaternal health (02/2022) (link)
• Covid-19 outbreaks on cancer comorbidities (10/2021) (link)
• Thyroid cancer health disparities (09/2021) (link)
• Role of obesity-induced cytokines on thyroid and breast cancer (08/2021) (link)
• Differential miRNA expression in thyroid cancer health disparities (06/2021) (link)
• (PEER REVIEWED) Davis R, Khan S. Differential miRNA signature in thyroid cancer helath disparities. AACR; San Francisco 2020. Kari Roberts, Choi SHK, Frank E, Foulad D, Mirhsahidi S, Perez MC, Simental AA, Firek AA, Khan S. Analysis of  differential Enigma gene expression in thyroid cancer vs. benign nodules. Endocrine Society Meeting 2020, San Francisco, CA. Choi SK, Roberts K, Frank E, Foulad D, Mirshahidi S, Perez M, Firek A, Simental A, Khan S. Analysis of Differential Enigma gene expression in thyroid cancer vs. benign nodules. J Invest. Med:68: DOI: 10.1136/jim-2019-WMRC.70; 2020 Frank E, Nyasani E, Chintalapati S, Perez MC, Munir I, Simental AA, Firek AA, Khan S. Upregulation of c-SRC/integrin in non-invasive and invasive human thyroid cancers: correlation with non-invasive and invasive phenotypes. American Thyroid Association, 2018, Washington DC. Santiago KR, Nyasani E, Wang H, Wongworawat YC, Perez MC, Munir I, Khan S. Differential expression of let-7 miRNA is thyroid cancer health disparities. Annual CHDMM symposium, 2018, Loma Linda, CA. Townsend M, Nyasani E, Perez MC, Mavingire N, Frank E, Chintalapati S, Wongworawat YC, Munir I, Firek AA, Khan S. Differential expressions of c-SRC and a-6 integrin in well-differentiated to poorly differentiated thyroid cancer. Annual CHDMM symposium, 2018, Loma Linda, CA. Cox B, Kim C, Chintalapati S, Mia C. Perez, Li L, Simental AA, Munir T, Munir I, Firek AA, Khan S. A novel differential subcellular expression pattern of a gene in well-differentiated thyroid cancer to anaplastic thyroid cancer. Basic Science Symposium, Loma Linda University, CA, USA 2017. Kim C, Chintalapati S, Mia C. Perez, Li L, Simental AA, Munir T, Munir I, Firek AA, Khan S. A novel differential subcellular expression pattern of a gene in anaplastic thyroid cancer compared to well-differentiated thyroid cancer. American Thyroid Association (ATA), Victoria BC, Canada, October 18-22, 2017. Chintalapati S, Mia C. Perez, Li L, Simental AA, Munir T, Munir I, Firek AA, Khan S. A novel differential subcellular expression pattern of a gene in anaplastic thyroid cancer compared to well-differentiated thyroid cancer. Pathology Meet, Loma Linda, 2017. Chintalapati S, Mia C. Perez, Li L, Simental AA, Munir T, Munir I, Firek AA, Khan S. A novel differential subcellular expression pattern of a gene in anaplastic thyroid cancer compared to well-differentiated thyroid cancer. APC, Loma Linda University, 2017. Khan S, Perez M, Chintalapati S, Lei L, Carr F, Simental A, Munir I, DeLeon M, Firek A.  A novel Oncoprotein Differentially Expresses from Well Differentiated to Undifferentiated Aggressive Phenotype. American Thyroid Association (ATA), Denver, CO, September 2016. (Selected for Short abstract). Nyasani E, Perez M, DeLeon M, Khan S. Vitamin D binding protein polymorphism in thyroid cancer health disparities.  CHDMM Annual Summer Symposium, August 2016, Loma Linda University, Loma Linda, CA. Monroe Q, Nyasani E, Perez M, Chintalapati S, Lei L, Perez M, Munir I, Firek A, DeLeon M, Khan S.Pathophysiological significance of Enigma oncoprotein in thyroid Cancer Gender disparities? CHDMM Annual Summer Symposium, August 2016, Loma Linda University, Loma Linda, CA. Lei L, Chintalapati S, Perez M, Munir I, Firek M, Khan S. Pathological significance of a novel oncoprotein expression in malignant thyroid nodules, not in benign nodules.  APC, Loma Linda University Medical Center, March 2016. Khan S, Stiff TR, Simpson J, Lynch JC, Leaf P, Gonda A, Casiano CA, Wall NR. Differential expression of stress proteins and miRNAs in circulating exosomes in prostate cancer health disparities. AACR Cancer Health Disparities Conference, Atlanta, GA, November 2015. Perez M, Nanda S, Perez M, Lei L, Munir I, DeLeon M, Khan S. Expression of vitamin D binding protein in thyroid cancer health disparities. Annual Health Disparities Symposium, Loma Linda University, Loma Linda, CA, August 2015. Khan S, Stiff TR, Lynch JC, Leaf P, Gonda A, Sanchez TW, Casiano CA, Wall NR. Exosomal surviving splice variants in prostate cancer health disparities. Endocrine Society meeting, San Diego, CA, April 2015. Mull B, Perez M, Lei L, Chowdhury S, Munir I, DeLeon M, Khan S. Differential expression of vitamin D binding protein in thyroid cancer health disparities. Annual Health Disparities Symposium, Loma Linda University, Loma Linda, CA, August 2014. Khan S, Turay D, Simpson J, Sanchez TW, Mirshahidi S, Casiano CA, Wall NR. Differential expression of inhibitors of apoptosis (IAP) protein releases in prostate cancer health disparities. Endocrine Society meeting, Chicago, IL, June 2014. Khan S, Turay D, Jutzy JMS, Aspe JR, Sanchez TW, Mirshahidi S, Casiano CA, Wall NR. Stress-induced differential Survivin release in prostate cancer health disparities. American Association of Cancer Research (AACR), San Diego, CA 2014. Osterman CJD, Valenzuela MMA, Bennit HRF, Khan S, Wall NR. Curcumin induces pancreatic cancer cell death by targeting IAPs. American Association of Cancer Research (AACR), San Diego, CA 2014. Valenzuela MMA, Bennit HRF, Osterman CJD, Khan S, Casiano CA, Wall NR. Survivin packaging into exosomes is lipid raft-dependent. American Association of Cancer Research (AACR), San Diego, CA 2014. Khan S, Yuan Y, Ferguson H, Wong SF, Perez M, Mirshahidi S, Wall NR.  Early diagnostic value of surviving and its alternative splice variants in breast cancer.  American Society of Clinical Oncology (ASCO) Breast Cancer Symposium, San Francisco, CA 2012. Khan S, Jutzy JMS, Aspe JR, and Wall NR.  Exosomal Survivin, a potential tool for early detection of pancreatic cancer health disparity?  B#97, AACR Pancreatic Cancer, Lake Tahoe, CA, 2012. Jackson NP, Khan S, and Wall NR.  Mechanism of Survivin Uptake in Cancer Cells.  Summer IMSD program, Loma Linda University 2011. Khan S, Jackson NP, Neidigh JW, and Wall NR.  Extracellular Survivin-Uptake by Cancer Cells.  Basic Science Symposium, Loma Linda University 2011. Khan S, Neidigh JW and Wall NR. Cellular import of the inhibitor of apoptosis (IAP) protein survivin. Proceedings of the American Association for Cancer Research, Abstract (#120) 2010. Khan S, Slater JM, Neidigh JW, and Wall NR. Characterization of an extracellular, cell permeable pool of the inhibitor of apoptosis (IAP) protein survivin. Proceedings of the American Association for Cancer Research, Abstract (#121) 2010. Slater JM, Khan S, Wall NR. Modulation of T Lymphocytes by Tumor-Released Survivin. Proceedings of the American Association for Cancer Research, Abstract (#4788) 2010. Pisarska MD, Bentsi-Barnes, I., Barlow, G., Khan S, Kuo F. "FOXL2 Mutations, Associated With Premature Ovarian Failure (POF), Likely Dimerize With Wild Type FOXL2, Leading to Altered Regulation Of Genes Associated With Granulosa Cell Differentiation". The Endocrine Society's 92nd Annual Meeting, San Diego, CA, 2010. Pisarska MD, Bentsi-Barnes, I, Barlow, G, Khan S, Kuo F. "LATS1 phosphorylates Forkhead L2 and regulates its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory Gene". The Endocrine Society's 91st Annual Meeting, Washington DC, 2009. Khan S, Asumen MG, Aspe JR, Almaguel F, Acevedo S, De Leon MN, Wall NR.  An extracellular, cell-permeable, pool of surviving has been found that provides protection against genotoxic stress upon its reabsorption into cancer cells.  Proceedings of the American Association for Cancer Research (AACR), 48:2008. Pisarska MD, Kuo F, Tang S, Khan S.  Forkhead L2 (FOXL2), A Gene Associated with Premature Ovarian Failure is Likely Regulated through Phosphorylation.  63rd Annual Meeting of the American Society for Reproductive Medicine, Washington DC, 2007. Kao LC, Lai H, Zhao Y, Pisarska MD, Khan S. Immunohistochemical demonstration of hormonal regulation of n-acetylglucosamine-6-o-sulfotransferase (GlcNAc-6-OST) in human endometrium. The Society for Gynecologic Investigation 53rd Annual Scientific Meeting, Toronto, Canada, March 2006. Khan S et al, FOXL2, a Gene Associated with Premature Ovarian Failure, Interacts with Large Tumor Suppressor Gene 1 (LATS1).  ASRM (American Society Of Reproductive Medicine) Abstract, New Orleans, Louisiana, 2006. Ketefian A, Khan S, Zarrini P, Kao L, Pisarska MD. Expression of forkhead transcription factors in the human granulosa cells. 62nd Annual Meeting of the American Society for Reproductive Medicine, New Orleans, LA, October 2006. Khan S et al, Immunohistochemical localization of N-acetylglucosamine-6-O sulfotransferase (GlcNAc-6-OST) in the human tissue microarray.  Society for Gynecological Investigation (SGI) meeting Toronto, Canada, March 22-25, 2006. Kumetz L, Khan S, Zarrini P, Trivax B, Kao L, Pisarska MD.  FoxL2, a gene associated with premature ovarian failure, interacts with large tumor suppressor gene 1 (Lats1) Abstract New Orleans, Louisiana, 2006. Khan S, et al. Hormonal regulation of N-acetylglucosamine-6-O-sulfotransferase (GlcNAc-6-OST) expression in a human endometrial cell model.  ASRM abstract P 770, Montreal, Canada, Oct 15-19, 2005. Ketefian A, Khan S, Zarrini P, Kao L, Pisarska MD.  P-712 Expression of forkhead transcription factors in human granulosa cells. American Society of Reproduction and Medicine (ASRM), Montreal, Canada, 2005. Mak W, Khan S, Pisarska MD, Kao L.  Androgen Suppression of a Target Human Implantation Gene N-acetylglucosamine-6-O-sulfotransferase (GlcNAc-6-OST) in a Human Endometrial Cell Model. American Society of Reproduction and Medicine (ASRM), Montreal, Canada, 2005. Bose S, Chandaran S, Khan S, Bose N.  Pathway of PTEN-signaling in breast cancer: a tissue array study.  American Association of Clinical Pathology (AACP) 2004. Khan S et al, In vivo and In vitro degradation of hCG by human macrophages.  Proceedings of 33rd Annual Meeting of Society for the Study of Reproduction (SSR), Madison, Wisconsin, USA, 2000. Khan S, et al Macrophage-conditioned media enhances the differentiation of cytotrophoblasts.  32nd Annual Meeting of Society for the Study of Reproduction (SSR), Pullman, Washington, USA, 1999. Khan S, et al, In vitro differentiation of cytotrophoblast by macrophage culture supernatant.  International Session (IS) in 51st Annual Congress of Japan Society of Obstetrics and Gynecology, Tokyo, Japan, 1999. Khan S, et al. In vivo and in-vitro differentiation of hCG by human peritoneal macrophages. IS in 50th Annual Congress on Japanese Society of Obstetrics and Gynecology, Sendai, Japan, 1998. Khan S, et al. In vivo and in-vitro differentiation of hCG by human peritoneal macrophages All Japan Society for Study of Lymphoreticular system, Kumamoto, Japan, 1998. Khan S, et al. Molecular forms of human chorionic gonadotropin in gestational trophoblastic diseases.  All Japan Congress on Placenta and Trophoblastic Diseases, Kumamoto, Japan, 1997. Ohtake H, Katabuchi H, Khan S, Tashiro H, In vitro model of endometriosis using ovarian surface epithelial cells and endometrial stromal cells.  48th Annual Congress of Japanese Society of Obstetrics and Gynecology, Tokyo, Japan, 1996.     Davis R, Khan S. Differential miRNA signature in thyroid cancer helath disparities. AACR; San Francisco 2020. Kari Roberts, Choi SHK, Frank E, Foulad D, Mirhsahidi S, Perez MC, Simental AA, Firek AA, Khan S. Analysis of  differential Enigma gene expression in thyroid cancer vs. benign nodules. Endocrine Society Meeting 2020, San Francisco, CA. (04/2020)
• (NON-PEER REVIEWED) Jackson NP, Khan S, and Wall NR.  Mechanism of Survivin Uptake in Cancer Cells.  Summer IMSD program, Loma Linda University 2011. Khan S, Jackson NP, Neidigh JW and Wall NR.  Extracellular Survivin-Uptake by Cancer Cells.  Basic Science Symposium, Loma Linda University 2011.   (04/2012)
• Expression of Fox-l2 in ovarian granulosa cells (04/2009) (link)

Online Publications

• Differential micro-RNA signatures in thyroid cancer subtypes Thyroid cancer is one of the most common endocrine cancers, with an increasing trend in the last few decades. Although papillary thyroid cancer is the most frequent subtype compared with follicular or anaplastic thyroid cancer, it can dedifferentiate to a more aggressive phenotype, and the recurrence rate is high. The cells of follicular adenomas and follicular carcinomas appear identical in cytology, making the preoperative diagnosis difficult. On the other hand, anaplastic thyroid cancer poses a significant clinical challenge due to its aggressive nature with no effective therapeutic options. In the past several years, the roles of genetic alterations of thyroid tumors have been documented, with a remarkable correlation between genotype and phenotype, indicating that distinct molecular changes are associated with a multistep tumorigenic process. Besides mRNA expression profiles, small noncoding microRNA (miRNA) expression also showed critical functions for cell differentiation, proliferation, angiogenesis, and resistance to apoptosis and finally activating invasion and metastasis in cancer. Several high-throughput sequencing studies demonstrate that miRNA expression signatures contribute clinically relevant information including types of thyroid cancer, tumor grade, and prognosis. This review summarizes recent findings on miRNA signatures in thyroid cancer subtypes. (12/2022) (link)

Scholarly Journals--Published

• Published:  Mull B, Davis R, Munir I, Perez MC, Simental AA, Khan S. Differential expression of vitamin D binding protein in thyroid cancer health disparities. Oncotarget 2021 Afroz S, Afroze T, Davis R, Khan S. Role of obesity-induced inflammatory cytokines on breast and thyroid cancer therapeutics: a literature review. J Cancer Biol Therap 2021. Walter S, Khan S. Building my Village 2021: Book chapter: Transgenerational aspects of Women in Medicine. Santiago K, Wongworawat CY, Khan S. Differential MicroRNA-signatures in thyroid cancer subtypes. J Oncol, 2020 Choi SK, Roberts K, Frank E, Foulad D, Mirshahidi S, Perez M, Firek A, Simental A, Khan S. Analysis of Differential Enigma gene expression in thyroid cancer vs. benign nodules. J Invest. Med:68: DOI: 10.1136/jim-2019-WMRC.70; 2020 (05/2021)
• Bennit H R F, Gonda A, Oppegard L J, Chi D P, Khan S, & Wall N R. (2017). Uptake of lymphoma-derived exosomes by peripheral blood leukocytes. Blood and Lymphatic Cancer-Targets and Therapy, 7, 9-23. Exosomes are nanosized lipid vesicles secreted into blood and other body fluids and serve as vehicles for intercellular communication. Despite being an important component of the tumor microenvironment (TME), exosomal targeting and uptake into recipient cells are still not fully understood. Few studies have looked at lymphoma exosomes and their interactions with circulating blood cells. In this study, we examine the exosomal uptake distribution among peripheral blood leukocytes (PBLs) using vesicles derived from a diffuse large B cell lymphoma cell line, WSU-DLCL2. Lymphoma cells survive, proliferate, and are protected from the cytotoxic effects of chemotherapeutic agents by soluble factors or by direct contact with inflammatory and stromal cells within the TME. In an attempt to close the gap in knowledge concerning lymphoma TME immunosuppression, we have treated normal human PBLs with PKH67-labeled lymphoma exosomes and monitored the uptake by measuring fluorescence at different time points using flow cytometry and fluorescent microscopy. Our results show that of the four populations examined, B cells and monocytes demonstrated uptake of PKH67-labeled exosomes, while T cells and NK cells displayed significantly less uptake. (2017) (link)
• Valenzuela M M, Ferguson Bennit H R, Gonda A, Diaz Osterman C J, Hibma A, Khan S, & Wall N R. (2015). Exosomes Secreted from Human Cancer Cell Lines Contain Inhibitors of Apoptosis (IAP). Cancer Microenviron, , . Exosomes are endosomal-derived nanovesicles released by normal and tumor cells which have been shown to transfer functionally active protein, lipids, mRNAs and miRNAs between cells. Varying in molecular profiles, biological roles, functional roles and protein contents, exosomes have been described as "multi-purpose carriers" playing a role in supporting the survival and growth of tumor cells. The IAP Survivin has been found to be present in tumor exosomes. However, the existence of other IAPs in tumor exosomes is still unknown. Survivin, cIAP1, cIAP2 and XIAP mRNA and protein are differently expressed in a panel of tumor cell lines: DLCL2, HeLa, MCF-7, Panc-1, and PC3. Exosomes were isolated from conditioned media collected from the cells from which RNA and protein were extracted. Our results provide evidence that like Survivin, XIAP, cIAP1 and cIAP2 proteins are found in tumor exosomes. The mRNA expression, however, is differentially expressed across the tumor cell lines. The presence of these bioactive molecules in exosomes may not only serve as warning signals, but also play a role in providing protection to the cancer cells against changes that are constantly occurring in the tumor microenvironment. (05/2015) (link)
• Khan S, Bennit FHR, Wall NR. The emerging role of exosomes in Survivin secretion. Histol & Histopathol, 30:43-50, 2015. (01/2015)
• Khan S, Bennit H F, & Wall N R. (2015). The emerging role of exosomes in survivin secretion. Histology and Histopathology, 30(1), 43-50. The tumor microenvironment plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Factors released by tumor cells themselves contribute in creating an environment mostly favorable but sometimes detrimental to the tumor. Survivin, one of the key members of the inhibitor of apoptosis (IAP) family of proteins, has been shown in the cytoplasm, mitochondria, nucleus, and most recently in the extracellular space, transported via small membrane bound vesicles called exosomes. Exosomes are secreted from hematopoietic, non-hematopoietic, tumor, and nontumor cells, shuttling essential molecules such as proteins, RNAs, and microRNAs, all believed to be important for cell-cell and cell-extracellular communication. In this review, we discuss exosomal Survivin and its role in modifying the tumor microenvironment. (01/2015)
• Khan S, Ferguson Bennit H, Asuncion Valenzuela M M, Turay D, Diaz Osterman C J, . . . Wall N R. (2015). Localization and upregulation of survivin in cancer health disparities: a clinical perspective. Biologics, 9, 57-67. Survivin is one of the most important members of the inhibitors of apoptosis protein family, as it is expressed in most human cancers but is absent in normal, differentiated tissues. Lending to its importance, survivin has proven associations with apoptosis and cell cycle control, and has more recently been shown to modulate the tumor microenvironment and immune evasion as a result of its extracellular localization. Upregulation of survivin has been found in many cancers including breast, prostate, pancreatic, and hematological malignancies, and it may prove to be associated with the advanced presentation, poorer prognosis, and lower survival rates observed in ethnically diverse populations. (2015) (link)
• Asuncion Valenzuela Malyn M, Castro Imilce, Gonda Amber, Diaz Osterman Carlos J, Jutzy Jessica M, . . . Wall Nathan R. (2015). Cell death in response to antimetabolites directed at ribonucleotide reductase and thymidylate synthase. OncoTargets & Therapy, 8, 495-507. New agent development, mechanistic understanding, and combinatorial partnerships with known and novel modalities continue to be important in the study of pancreatic cancer and its improved treatment. In this study, known antimetabolite drugs such as gemcitabine (ribonucleotide reductase inhibitor) and 5-fluorouracil (thymidylate synthase inhibitor) were compared with novel members of these two drug families in the treatment of a chemoresistant pancreatic cancer cell line PANC-1. Cellular survival data, along with protein and messenger ribonucleic acid expression for survivin, XIAP, cIAP1, and cIAP2, were compared from both the cell cytoplasm and from exosomes after single modality treatment. While all antimetabolite drugs killed PANC-1 cells in a time- and dose-dependent manner, neither family significantly altered the cytosolic protein level of the four inhibitors of apoptosis (IAPs) investigated. Survivin, XIAP, cIAP1, and cIAP2 were found localized to exosomes where no significant difference in expression was recorded. This inability for significant and long-lasting expression may be a reason why pancreatic cancer lacks responsiveness to these and other cancer-killing agents. Continued investigation is required to determine the responsibilities of these IAPs in their role in chemoresistance in pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR] Copyright of OncoTargets & Therapy is the property of Dove Medical Press Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) (2015) (link)
• Khan Salma, Bennit Heather Ferguson, Turay David, Perez Mia, Mirshahidi Saied, Yuan Yuan, & Wall Nathan R. (2014). Early diagnostic value of survivin and its alternative splice variants in breast cancer. Bmc Cancer, 14(1), 1-10. Background: The inhibitor of apoptosis (IAP) protein Survivin and its splice variants are differentially expressed in breast cancer tissues. Our previous work showed Survivin is released from tumor cells via small membrane-bound vesicles called exosomes. We, therefore, hypothesize that analysis of serum exosomal Survivin and its splice variants may provide a novel biomarker for early diagnosis of breast cancer. Methods: We collected sera from forty breast cancer patients and ten control patients who were disease free for 5 years after treatment. In addition, twenty-three paired breast cancer tumor tissues from those same 40 patients were analyzed for splice variants. Serum levels of Survivin were analyzed using ELISA and exosomes were isolated from this serum using the commercially available ExoQuick kit, with subsequent Western blots and immunohistochemistry performed. Results: Survivin levels were significantly higher in all the breast cancer samples compared to controls (p < 0.05) with exosome amounts significantly higher in cancer patient sera compared to controls (p < 0.01). While Survivin and Survivin-Î?Ex3 splice variant expression and localization was identical in serum exosomes, differential expression of Survivin-2B protein existed in the exosomes. Similarly, Survivin and Survivin-Î?Ex3 proteins were the predominant forms detected in all of the breast cancer tissues evaluated in this study, whereas a more variable expression of Survivin-2B level was found at different cancer stages. Conclusion: In this study we show for the first time that like Survivin, the Survivin splice variants are also exosomally packaged in the breast cancer patients' sera, mimicking the survivin splice variant pattern that we also report in breast cancer tissues. Differential expression of exosomal-Survivin, particularly Survivin-2B, may serve as a diagnostic and/or prognostic marker, a "liquid biopsy" if you will, in early breast cancer patients. Furthermore, a more thorough understanding of the role of this prominent antiapoptotic pathway could lead to the development of potential therapeutics for breast cancer patients. [ABSTRACT FROM AUTHOR] Copyright of BMC Cancer is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) (2014) (link)
• Khan S, Jutzy J M S, Valenzuela M M A, Turay D, Aspe J R, . . . Wall N R. (2012). Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer. Plos One, 7(10), . Background: Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents in vitro and in vivo. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment. Methods: Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively. Results: Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls. Conclusions: These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection. (10/2012) (link)
• J.M.S. Jutzy, S. Khan, M.M.A. Valenzuela, T.M. Milford, K.J. Payne, N.R. Wall. Tumor-released Survivin induces a type-2 T cell response and decreasesâ?¨cytotoxic T cell function, in vitro.  Cancer Microenvironment 2012 (In press). S. Khan, J.M.S Jutzy, J.R. Aspe, M.M.A Valenzuela, J. Park, D. Turay, N.R. Wall. Application of Membrane Vesicles for Cancer Therapy. Advances in Cancer Therapy ISBN 979-953-307-209-7, (2011) S. Khan, J.M.S Jutzy, J.R Aspe, D.W. McGregor, J.W Neidigh, N.R Wall. Survivin is released from cancer cells via exosomes. Apoptosis 16(1): 1-12, (2011). (04/2012)
• Jutzy J M, Khan S, Asuncion-Valenzuela M M, Milford T A, Payne K J, & Wall N R. (2012). Tumor-Released Survivin Induces a Type-2 T Cell Response and Decreases Cytotoxic T Cell Function, in Vitro. Cancer Microenviron, , . Clinical studies of T cell profiles from cancer patients have shown a skewing toward a type-2 T cell response with decreased cytotoxic T cell function. However, the primary cause of this shift remains unknown. Here we show that tumor-released Survivin, an inhibitor of apoptosis (IAP) protein and tumor-specific antigen, is taken up by T cells and alters their response. The addition of Survivin to T cell cultures resulted in decreased T cell proliferation and reduced cytotoxic CD8(+) T cell function. Additionally, type 1 cell numbers and IFN-gamma and IL-2 production were significantly reduced, while IL-4 release and type 2 T cell numbers increased. In contrast, the function and numbers of Th17 and T regulatory cells were not affected. These studies show that tumor-released Survivin modulates T cells resulting in a phenotype similar to that observed in cancer patients with a polarity shift from a type 1 to a type 2 response. (02/2012) (link)
• Khan S, Jutzy J M, Aspe J R, McGregor D W, Neidigh J W, & Wall N R. (2011). Survivin is released from cancer cells via exosomes. Apoptosis, 16(1), 1-12. Inhibitor of apoptosis (IAP) and Heat shock proteins (HSPs) provide assistance in protecting cells from stresses of hypoxia, imbalanced pH, and altered metabolic and redox states commonly found in the microenvironmental mixture of tumor and nontumor cells. HSPs are upregulated, cell-surface displayed and released extracellularly in some types of tumors, a finding that until now was not shared by members of the IAP family. The IAP Survivin has been implicated in apoptosis inhibition and the regulation of mitosis in cancer cells. Survivin exists in a number of subcellular locations such as the mitochondria, cytoplasm, nucleus, and most recently, the extracellular space. Our previous work showing that extracellular survivin was able to enhance cellular proliferation, survival and tumor cell invasion provides evidence that Survivin might be secreted via an unidentified exocytotic pathway. In the present study, we describe for the first time the exosome-release of Survivin to the extracellular space both basally and after proton irradiation-induced stress. To examine whether exosomes contributed to Survivin release from cancer cells, exosomes were purified from HeLa cervical carcinoma cells and exosome quantity and Survivin content were determined. We demonstrate that although proton irradiation does not influence the exosomal secretory rate, the Survivin content of exosomes isolated from HeLa cells treated with a sublethal dose of proton irradiation (3 Gy) is significantly higher than control. These data identify a novel secretory pathway by which Survivin can be actively released from cells in both the basal and stress-induced state. (01/2011) (link)

Book Review - Scholarly Journals--Published

• 1. Walter S, Khan S. Building my Village 2021: Book chapter: Transgenerational aspects of Women in Medicine. 2. A clinical guide on COVID-19 treatment: A clinical Perspective: COVID-19 Vaccine: edited by Dr. Chowdhury Ahsan, MD/Ph.D. 2. Yousef S, Simental AA, Khan S. Proteomic profiling of tumor exosomes. Exosomes in Cancer; Diagnostic, Pharmaceutical and Therapeutic Applications. Editors: Amiji MM & Ramesh R. Published 2018.   (04/2021)

Books and Chapters

• H. Katabuchi, H. Ohtake, S. Khan, Y. Fukumatsu, H. Okamura Macrophages in Reproductive Organs.  In:  PM Motta (ed.) Recent Advances in Microscopy in Reproductive System.  Rome:  Antonio Delfino Editore: 547-552 (1997). S. Khan, Jutzy JMS, Aspe JR, Turay D, Wall NR.  The Application of Membrane Vesicles for Cancer Therapy.  Advances in Cancer Therpay ISBN 979-953-307-209-7: 21-39 (2011).   (04/2012)

Scholarly Journals--Submitted

• S. Khan, J.M.S. Jutzy, D. Turay, M.M.A. Valenzuela, M.B. Lilly, and N.R. Wall.  The Inhibitor of Apoptosis (IAP) Protein Survivin Exists in the Serum Exosomes of Mid and Advanced Stage Prostate Cancer Patients.  (Submitted).   (04/2012)