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The PARP-1 Inhibitor Olaparib Causes Retention of γ-H2AX Foci in <i>BRCA</i>1 Heterozygote Cells Following Exposure to Gamma Radiation

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Journal of Cancer Therapy 2013年第11期4卷 44-52页

作者： Emma C. Bourton Piers N. Plowman Amanda J. Harvey sheba adam zahir Christopher N. Parris Brunel Institute of Cancer Genetics and Pharmacogenomics Division of Biosciences School of Health Sciences and Social Care Brunel University Uxbridge UK Department of Radiotherapy St Bartholomew’s Hospital West Smithfield London UK

A novel treatment for cancer patients with homozygous deletions of BRCA1 and BRCA2 is to use drugs that inhibit the enzyme poly(ADP-ribose) polymerase (PARP). Specific inhibition of PARP-1 can induce synthetic lethality in irradiated cancer cells while theoretically leaving normal tissue unaffected. We recently demonstrated in a cell survival assay that lymphoblastoid cells with mono-allelic mutations of BRCA1 were hypersensitive to gamma radiation in the presence of the PARP-1 inhibitor Olaparib compared to normal cells and mono-allelic BRCA2 cells. To determine if the enhanced radiation sensitivity was due to a persistence of DNA strand breaks, we performed γ-H2AX foci analysis in cells derived from two normal individuals, three heterozygous BRCA1 and three heterozygous BRCA2 cell lines. Cells were exposed to 2 Gy gamma radiation in the presence or absence of 5 μM Olaparib. Using immunofluorescence and imaging flow cytometry, foci were measured in untreated cells and at 0.5, 3, 5 and 24 hours post-irradiation. In all lymphoblastoid cells treated with 2 Gy gamma radiation, there was a predictable induction of DNA strand breaks, with a modest but significant retention of foci over 24 hours in irradiated cells treated with Olaparib (ANOVA P < 0.05). However, in mono-allelic BRCA1 cells, there was a failure to fully repair DNA double-strand breaks (DSB) in the presence of Olaparib, evidenced by a significant retention of foci at 24 hours’ post irradiation (t-Test P These data show that the cellular hypersensitivity of mono-allelic BRCA1 lymphoblastoid cells to gamma radiation in the presence of the Olaparib is due to the retention of DNA DSB. These data may indicate that patients with inherited mutations in the BRCA1 gene treated with radiotherapy and PARP-1 inhibitors may experience elevated radiation-associated normal tissue toxicity.

关键词： BRCA1 BRCA2 Heterozygote Radiosensitivity PARP Inhibitor Gamma-H2AX Imaging Flow Cytometry

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Sperm fine-needle aspiration (FNA)mapping after failed microdissection testicular sperm extraction (TESE):location and patterns of found sperm

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Asian Journal of Andrology 2019年第1期21卷 50-55页

作者： sheba Jarvis Heather K Yee Natalia Thomas Imok Cha Kedar Che Prasad Jonathan W A Ramsay Paul J Turek Imperial College London Hammersmlth HospitalLondon W12 ONNUK The Turek Clinic San FranciscoCA 94133USA Marin Medical Laboratories Greenbrae CA 94904USA.

We sought to evaluate the ability of fine-needle aspiration (FNA)mapping to find sperm and to guide sperm retrieval after failed microdissection testicular sperm extraction (micro-TESE)in nonobstructive azoospermic *** this study of consecutive male infertility cases,interventions included testicular FNA mapping and subsequent sperm *** included the frequency and location of found sperm on FNA maps after failed micro-TESE and the salvage sperm retrieval *** 548 patients undergoing FNA mapping from 2010 to 2016,82 men with previous micro-TESE procedures were *** mean time between micro-TESE and FNA mapping was 2.2 years.A total of 2825 (1424 on right and 1401 on left)sites were *** least one site revealed mature sperm in 24 (29.3%)of 82 men with prior failed micro-TESE *** was an equal likelihood of detecting sperm in either testis (6.1%right;5.7%left;P=0.58).Digital "heat maps"revealed differences in sperm findings within the testis with mature sperm more likely found in the testis periphery rather than *** (62.5%)patients subsequently underwent sperm retrieval procedures guided by FNA *** sperm were retrieved in all cases,and in 10 (66.7%)of 15 cases,extra sperm were frozen for future *** a significant proportion of failed micro-TESE procedures representing the largest study to date,sperm were detected by FNA mapping and could be reliably retrieved through FNA map-guided surgical sperm *** present,sperm were more likely to be found in the testis periphery rather than centrally with FNA mapping.

关键词： azoospermia hypogonadism IVF-ICSI microdissection TESE sperm FNA mapping sperm retrieval

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Maternal Outcome of Cases of Placenta Previa with and without Morbidly Adherent Placenta at King Abdul-Aziz University Hospital, Saudi Arabia

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Open Journal of Obstetrics and Gynecology 2018年第13期8卷 1414-1422页

作者： Ashraf Radwan Abdel Magid Abdou Sausan Kafy Mamdouh sheba Hassan Allam Moaz Bokhari Majed Almutairi Department of Obstetrics and Gynecology King Abdul-Aziz University Rabigh Branch Rabigh KSA Department of Obstetrics and Gynecology King Abdul-Aziz University Hospital Jeddah KSA

Introduction:?Worldwide increasing cesarean section rates are expected to have a parallel increase in the number of cases of Placenta Previa with all the expected complications, including pathologically adherent placenta. This morbidly adherent placenta constitutes a serious and possibly a life threatening complication. An efficient team capable for managing possible complicated situations will be able to reduce mortality and morbidity. Objectives: The aim of our study was to evaluate maternal outcome in cases of Placenta Previa with and without morbidly adherent placenta. Methods: Analysis of all pregnancies complicated by antepartum hemorrhage during the period from January 2013 to September 2017 at King Abdul-Aziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia (KSA) was done. Cases of Placenta Previa with gestational age > 28 weeks were included. They were classified into 2 groups;Group (A) included Placenta Previa cases without morbidly adherent placenta and Group (B) included cases with morbidly adherent placenta. Maternal outcomes were recorded. Results: Placenta Previa was the leading cause of antepartum hemorrhage constituting 76.8%, out of them 52% were unbooked. Morbidly adherent placenta constituted 13.5% of total Placenta Previa cases and was diagnosed prenatally in only 1 case. Morbidity rate in placenta previa patients with adherent placenta (Group B) was higher than in placenta previa without adherent placenta (Group A). We considered the occurrence of intrapartum hypovolemic shock, Intensive care unit admission, surgical complications and peripartum hysterectomy as parameters for morbidity. P value for hypovolemic shock was insignificant (P = 0.580), significant for Intensive care unit admission (P = 0.008), significant for surgical complications (P = 0.009) and significant for peripartum

关键词： Maternal Outcomes Placenta Previa With and without Adherent Placenta

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妊娠期恶心与呕吐的管理

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英国医学杂志中文版 2011年第5期14卷 290-295页

作者： sheba Jarvis Catherine Nelson-Piercy 吕涛（译）廖琴平（校） Imperial College Healthcare NHS Trust Hammersmith Hospital London WI2 0NN UK Guys and St Thomas NHS Fotmdafion Trust London SE1 7EH UK 北大医院妇产科

恶心呕吐是妊娠期最常见的症状。因此许多医疗工作者都会遇到这个问题，也应当熟悉如何进行适当的观察和当前推荐的治疗方式。妊娠女性中50％～90％会出现恶心呕吐，并且其中35％的女性在躯体和心理方面均需要医疗干预。尽管我们通俗称... 详细信息

恶心呕吐是妊娠期最常见的症状。因此许多医疗工作者都会遇到这个问题，也应当熟悉如何进行适当的观察和当前推荐的治疗方式。妊娠女性中50％～90％会出现恶心呕吐，并且其中35％的女性在躯体和心理方面均需要医疗干预。尽管我们通俗称其为“晨吐”，但实际上在很多女性症状会持续一整天，从偶尔发生到剧烈且难治性呕吐均存在。恶心呕吐始于早孕期6—8周的时候，一般在第9周达到高峰，

关键词：恶心呕吐妊娠期管理医疗工作者难治性呕吐治疗方式医疗干预心理方面

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Envita’s Precision Cancer Care: 35-Fold Improvement in Response Rates

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Journal of Cancer Therapy 2024年第4期15卷 99-120页

作者： sheba Goklany John C. Oertle III Ronald Matthias Jr. Daniel Warren David Medina Rory Sears Robert Zieve Kendra Quart Christopher Aussems Jon Moma Shannon Miller Zach Poteet Conner Coffin Courtney Middleton Erika Ware Phylicia Zarnosky Julie Nowak Winlove Suasin Daniel Conway Chad Burk Ruth Tan-Lim Dino Prato Envita Medical Centers Scottsdale AZ USA

New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.

关键词： Envita Medical Centers Late-stage Cancer Overall Response Rate Quality of Life Circulating Tumor Cells (CTCs) Mutant Allele Frequency (MAF) Precision Care

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