tbuckley/cabot-search huggingface dataset:
Abstract 916: Slit2 inhibits breast cancer growth and metastasis by modulating tumor microenvironment
Authors: Dinesh K. Ahirwar, Mohd W. Nasser, Mohamad Elbaz, Kontestine Shilo, Ramesh Ganju
Journal: Cancer Research (2016)

Abstract Breast cancer (BC) continues to be a major health issue particularly in developed countries. The Slit2 gene is hyper-methylated in BC and acts through Roundabout Homolog1 (Robo1) receptor. Slit2/Robo1 signaling has been shown to inhibit the migration of a variety of cells including BC cells. Recently, it has also been reported to improve chemotherapy outcome in intestinal cancer. However, Slit2/Robo1-mediated mechanisms that regulate tumor growth and metastasis are not well known. Using syngeneic mouse model, we report that the over-expression of Slit2 using Adeno-Slit2 transduction successfully restrains tumor growth and also restrict the metastasis to lung, compared to Adeno-null control. To explore the Slit2 mediated cellular events, we analyzed the stromal cells recruitment to the tumor and observed reduced number of tumor associated macrophages (TAMs) in the Adeno-Slit2 group compared to Adeno-null group. We further analyzed the underlying molecular mechanisms and found that the soluble Slit2 inhibits TGF-β1 mediated alternative activation of macrophages to TAMs. Treatment with TGF-β1 significantly enhances the markers of TAMs by upregulating β-catenin levels. Interestingly, we observed that Soluble Slit2 inhibits TGF-β1 mediated activation of TAMs by inhibiting downstream signaling molecules Smad2 and β-catenin. We also analyzed Slit2 expression in human breast cancer TMA and an inverse correlation of Slit2 expression was observed with the incidence of breast cancer, metastasis and macrophage recruitment. This study highlights the ability of Slit2 to prevent macrophage alternative activation to TAMs, thereby restrict tumor growth and lung metastasis. Anti-cancer activity of Adeno-Slit2 suggests therapeutic potential of Slit2 to treat advanced breast cancer. Citation Format: Dinesh K. Ahirwar, Mohd W. Nasser, Mohamad Elbaz, Kontestine Shilo, Ramesh Ganju. Slit2 inhibits breast cancer growth and metastasis by modulating tumor microenvironment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 916.
Piperacillin/tazobactam monotherapy versus combination ceftazidime plus amikacin for the treatment of febrile neutropenia in patients with cancer: A Hellenic Co-Operative Oncology Group Study
Authors: D. Pectasides, G. Fountzilas, G. Samonis, D. Panidis, I. Grimani, D. Bafaloukos, N. Pavlidis, M. Pectasides, S. Kyroudi-Markantoni, G. Aravantinos
Journal: Journal of Clinical Oncology (2006)

18590 Background: Combinations of β-lactam antibiotics and aminoglycosides are considered standard therapy for febrile neutropenia. Monotherapies have been proposed as standard treatments, demonstrating equal efficacy and better safety. Methods: This is a prospective, multi-centre, randomized clinical trial. Cancer patients with absolute neutrophil count (ANC) &lt;1,000/mm 3 and fever &gt;38 o C for ≥ 2 hours were randomized to either piperacillin/tazobactam 4.5 g every 8 h i.v. (group A) or ceftazidime 2 g every 8 h plus amikacin 15 mg/kg i.v. per day (group B). In case of fever &gt;38 o C 48 h after initiation of the therapy, vancomycin 500 mg every 6 h i.v. was added. Minimal duration of treatment was 72 hours. Treatment was continued for 7 days in case of improvement, otherwise vancomycin was added or the study therapy was discontinued. Early efficacy was assessed on day 3 and overall response 4 days after the end of treatment. Complete success was defined the patient to become afebrile and no other antibiotics to be added. Treatment failures were classified in two categories, those in which vancomycin was added to the study regimen, and those in which other antibiotics were used. Categorical variables were compared between treatment groups with the use of Fisher’s exact test, while for continuous Wilcoxon’s rank sum test was used. Results: One hundred twenty-seven febrile episodes were treated (group A: 66, group B: 61). Patient characteristics were well balanced in terms of age, underlying malignancies, ANC, and granulocyte-colony stimulating factor (G-CSF) support. Both treatments were well tolerated. No significant differences were seen in terms of success to treatment. Complete success was achieved in 45 (68%) of patients in group A and 40 (66%) in group B, while another 8 patients in group A (12%) and 6 in group B (10%) required addition of pre-defined anti-staphyloccocci antibiotic. Conclusions: Empirical treatment of febrile neutropenic episodes with piperacillin/tazobactam monotherapy appears to be as effective as the “standard” ceftazidime/amikacin combination. No significant financial relationships to disclose.
Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0): Recommendations for Standardized FDG-PET/CT Experiments in Humans
Authors: Kong Y. Chen, Aaron M. Cypess, Maren R. Laughlin, Carol R. Haft, Houchun Harry Hu, Miriam A. Bredella, Sven Enerbäck, Paul E. Kinahan, Wouter van Marken Lichtenbelt, Frank I. Lin, John J. Sunderland, Kirsi A. Virtanen, Richard L. Wahl
Journal: Cell Metabolism (2016)
Abstract 1542: Identification and utilization of molecular pathways correlated with osteosarcoma metastasis to predict targeted therapies
Authors: Laird Klippenstein, Jared S. Fowles, Sierra K. Lear, Daniel L. Gustafson
Journal: Cancer Research (2016)

Abstract Osteosarcoma (OSA) is the most prevalent primary bone tumor and accounts for approximately 2% of childhood cancers. Approximately 40% of all OSA patients succumb to metastatic disease within 5 years. Canine OSA occurs about 10 times more frequently than human OSA and has been shown to be very similar to pediatric OSA biologically, histologically, molecularly, and in treatment. This suggests that canine OSA is an excellent pre-clinical model to investigate better treatment options for metastatic OSA. We compared in-vitro markers of metastatic potential with gene expression data in eight canine OSA cell lines to identify molecular pathways that will be potential chemotherapeutic targets to treat and prevent metastatic OSA. The metastatic potential of 8 canine OSA cell lines was characterized utilizing Incucyte Zoom based migration and invasion scratch wound assays. Gene expression analysis was performed using Affymetrix GeneChip Canine Genome 2.0 Arrays. Genes that were statistically correlated with migratory and invasive phenotypes were used to enrich molecular pathways described in several databases utilizing Enrichr software. Altered pathways and associated targeted agents that would inhibit the pathways enriched by the correlated gene sets were identified. Chemotherapeutics targeting significantly enriched pathways were screened for their ability to inhibit metastatic potential. Dasatinib and Stattic were the only inhibitors screened to date that inhibit migration of the osteosarcoma cell lines at clinically relevant doses. The remaining significantly correlated pathways will be targeted as well as rational combinations of pathways. An orthotopic murine model is currently being tested to further explore the utility of efficacious chemotherapeutics in-vivo. Pathway Inhibition and Anti-Migratory EffectsPathwayP-ValueTargeted AgentIC50 vs MigrationMap Kinase0.0037Selumetinib&amp;gt;25 uM *Focal Adhesion0.0059Dasatinib18 nM - 214 nMErbb2/30.0214Lapatinib&amp;gt;8 uM *TubulinControlPaclitaxel7 nM - 54 nMmTOR0.0054Rapamycin&amp;gt;20 nM *STAT30.0004Stattic2.4 uM - 4.6 uMBMPR2&amp;lt;0.0005Tacrolimus&amp;gt;12.5 nM *ALK&amp;lt;0.0005Crizotinib&amp;gt;900 nM *VEGFR0.0226VandetanibTBDITK&amp;lt;0.0005IbrutinibTBDPDPK10.0011CelecoxibTBD* We were not able to reach an IC50 at clinically relevant doses Citation Format: Laird Klippenstein, Jared S. Fowles, Sierra K. Lear, Daniel L. Gustafson. Identification and utilization of molecular pathways correlated with osteosarcoma metastasis to predict targeted therapies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1542.
Abstract 2812: Targeting reactive oxygen species in human cancer cell growth and metastasis in nude mouse
Authors: Haruhiko Inufusa
Journal: Cancer Research (2016)

Abstract [Purposes of the study] Reactive oxygen species (ROS) are associated with clinical condition, and closely involved in cancer growth and metastasis. Twendee X is a composition consisting of Vitamin C, Glutamine, Cystine, Riboflavin, Succinic acid, Fumaric acid, Coenzyme Q10, and Niacin. Twendee X strongly reduces oxygen radicals or ROS in vitro and in vivo (World Intellectual Property Organization WO/2013/072441 COMPOSITION FOR PROTECTION AGAINST CELL-DAMAGING EFFECTS). Effects of Twendee X on human colon cancer cell lines growth and metastasis in nude mouse was examined. [Experimental procedures] Human colon cancer cell line RPMI4788 human gastric cancer cell line MKN45 was used in this study. Ten nude mice (BALB/C nu-nu, 4wks, Male) per each group of experiments were used, and repeated twice. Two cell lines were inoculated in subcutaneous of nude mouse, and tumor growth monitored for days. Lung metastasis was counted weeks after injection RPMI4788 cells into the tale vein of nude mouse. Twendee X was added to the free drink water around 37mg/kg/day by calculation. Serum of tumor bearing nude mouse was sampled just before sacrifice. Free Calpe Diem (Diacron International, Italy) was used to measure ROS related marker d-ROMs test (detect hydrogen peroxide). Natural Killer cell (NK) activity also measured in tumor bearing nude mouse. [Data] Tumor growth of RPMI4788 and MKN45 was reduced 25% and 40% respectively by Twendee X administration. Metastatic nodule of RPMI4788 was reduced to 1/7 by Twendee X administration. Increase value of d-ROMs test reduced to 60% compare to the control by Twendee X administration. NK activity of RPMI4788 tumor bearing nude mouse was reduced to 28% compare to the normal mouse, and increased to 56% by Twendee X administration. [Conclusion] Twendee X has significant effects of reducing tumor growth and inhibition metastasis. Hydrogen peroxide level (d-ROMs test) of tumor bearing nude mouse in serum was significantly reduced. ROS effects on immune cell activity, and Twendee X recovered suppressed NK activity. Thus, Twendee X effects on ROS inhibition and suppressed RPMI 4788 tumor growth and metastasis to the lung of nude mouse. Metastatic nodules receiving larger blood flow compare to the tumor in the back of mouse, thus means anti-tumor immune cells in blood may easier attack cancer cells. Citation Format: Haruhiko Inufusa. Targeting reactive oxygen species in human cancer cell growth and metastasis in nude mouse. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2812.
Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma
Authors: Anita Kumar, Carla Casulo, Joachim Yahalom, Heiko Schöder, Paul M. Barr, Philip Caron, April Chiu, Louis S. Constine, Pamela Drullinsky, Jonathan W. Friedberg, John F. Gerecitano, Audrey Hamilton, Paul A. Hamlin, Steven M. Horwitz, Alexandra G. Jacob, Matthew J. Matasar, Gianna N. McArthur, Susan J. McCall, Alison J. Moskowitz, Ariela Noy, Maria L. Palomba, Carol S. Portlock, David J. Straus, Nicholas VanderEls, Stephanie L. Verwys, Joanna Yang, Anas Younes, Andrew D. Zelenetz, Zhigang Zhang, Craig H. Moskowitz
Journal: Blood (2016)
P1006 : Liver iron concentration in the metabolic syndrome with hyperferritinemia (dysmetabolic hyperferritinemia). Results from a cohort of patients studied by MRI
Authors: E. Zapata, A. Castiella, L. Zubiaurre, A. Iribarren, J.M. Alustiza, E. Salvador, J.I. Emaparanza, P. Otazua
Journal: Journal of Hepatology (2015)
Enhanced surveillance of carbapenemase-producing Gram-negative bacteria to support national and international prevention and control efforts
Authors: R Freeman, D Ironmonger, R Puleston, K L Hopkins, W Welfare, R Hope, P Staves, M Shemko, S Hopkins, P Cleary, B Patel, B Muller-Pebody, X Li, A Alvarez-Buylla, P M Hawkey, A P Johnson, N Woodford, I Oliver
Journal: Clinical Microbiology and Infection (2016)
Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity
Authors: Tatsuma Ban, Go R. Sato, Akira Nishiyama, Ai Akiyama, Marie Takasuna, Marina Umehara, Shinsuke Suzuki, Motohide Ichino, Satoko Matsunaga, Ayuko Kimura, Yayoi Kimura, Hideyuki Yanai, Sadakazu Miyashita, Junro Kuromitsu, Kappei Tsukahara, Kentaro Yoshimatsu, Itaru Endo, Tadashi Yamamoto, Hisashi Hirano, Akihide Ryo, Tadatsugu Taniguchi, Tomohiko Tamura
Journal: Immunity (2016)

Interferon regulatory factor-5 (IRF5), a transcription factor critical for the induction of innate immune responses, contributes to the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) in humans and mice. Lyn, a Src family kinase, is also implicated in human SLE, and Lyn-deficient mice develop an SLE-like disease. Here, we found that Lyn physically interacted with IRF5 to inhibit ubiquitination and phosphorylation of IRF5 in the TLR-MyD88 pathway, thereby suppressing the transcriptional activity of IRF5 in a manner independent of Lyn's kinase activity. Conversely, Lyn did not inhibit NF-κB signaling, another major branch downstream of MyD88. Monoallelic deletion of Irf5 alleviated the hyperproduction of cytokines in TLR-stimulated Lyn–/– dendritic cells and the development of SLE-like symptoms in Lyn–/– mice. Our results reveal a role for Lyn as a specific suppressor of the TLR-MyD88-IRF5 pathway and illustrate the importance of fine-tuning IRF5 activity for the maintenance of immune homeostasis.
Abstract 1272: Inhibition of Nuclear Factor-Kappa B Improves Endoplasmic Reticulum Stress-Induced Apoptosis and LV Remodeling in Heart Failure
Authors: Tariq Hamid, Xilin Xiang, James P Marshall, Ernest M Cardwell, Buddhadeb Dawn, Sumanth D Prabhu
Journal: Circulation (2007)

The endoplasmic reticulum (ER) normally participates in protein folding, calcium storage, and cell signaling. Cellular insult, however, induces the ER-stress response that can produce apoptosis and cell death with persistent activation. Nuclear factor (NF)-κB, a transcriptional regulator of cell survival responses is implicated in the maladaptive responses of ER-stress. However, its role in modulating ER stress-responses in the failing heart is unknown. Hypothesis: NF-κB activation in heart failure (HF) exacerbates LV remodeling in part by augmenting maladaptive ER-stress responses. Coronary ligation (or sham operation) was performed in male transgenic (TG) mice with cardiac-specific overexpression of a dominant-negative (DN) IκBα (n=16) and in non-transgenic (NTG) littermates (n=16). Compared to NTG sham, 4 weeks after surgery, NTG HF hearts exhibited significant (p &lt; 0.05): LV dilatation and systolic dysfunction; myocyte hypertrophy and fibrosis; and NF-κB activation (~2-fold). Immunoblotting also revealed reduced expression (p &lt; 0.05) of ER resident chaperones Grp78 and Grp94 and increased expression (p &lt; 0.001) of CHOP, a pro-apoptotic transcription factor induced by ER stress, that correlated with increased (p &lt; 0.05) apoptosis by TUNEL staining (1.1 ± 0.5 vs. 0.03 ± 0.03%, p &lt; 0.05)). In contrast, compared to NTG HF, TG HF hearts had markedly reduced (p &lt; 0.01) NF-κB activation, significantly less (p &lt;0.05) LV dilatation, systolic dysfunction, and fibrosis but similar degrees of myocyte hypertrophy. Importantly, NF-κB abrogation also resulted in significantly increased expression of Grp78 and Grp94 and complete prevention of CHOP induction. Also, compared to TG sham, TG HF showed a mild but non-significant (p &lt;0.45) increase in apoptotic rates (0.4 ± 0.3 %) by TUNEL. Parallel H9c2 cell studies indicated that induction of ER stress with tunicamycin activated NF-κB and increased apoptosis as measured by caspase-3, -12, and PARP cleavage. In contrast, DN IκBα adult cardiomyocytes maintained viability upon tunicamycin exposure suggesting a pro-apoptotic role for NF-κB activation during ER stress. Conclusion: Persistent NF-κB activation in post-infarction HF exacerbates cardiac ER stress and apoptosis and worsens LV remodeling.
Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer
Authors: Tzu-Yin Lin, Yuanpei Li, Qiangqiang Liu, Jui-Lin Chen, Hongyong Zhang, Diana Lac, Hua Zhang, Katherine W. Ferrara, Sebastian Wachsmann-Hogiu, Tianhong Li, Susan Airhart, Ralph deVere White, Kit S. Lam, Chong-Xian Pan
Journal: Biomaterials (2016)
Abstract 1925: Regulation of metabotropic glutamate receptor 5 expression by the miR-30 downregulation induced by the SDF-1/CXCR4 system in oral cancer cells
Authors: Nobuyuki Kuribayashi, Daisuke Uchida, Makoto Kinouchi, Chikako Koshiji, Sayaka Izumi, Kembun Hakata, Yuske Komiyama, Shuji Tsuchida, Tomonori Hasegawa, Hitoshi Kawamata
Journal: Cancer Research (2016)

Abstract We have previously demonstrated that stromal cell-derived factor (SDF)-1/CXCR4 system enhances the metastases of oral cancer cells via induction of metabotropic glutamate receptor (mGluR) 5. However, the mechanism(s) of mGluR5 expression induced by the SDF-1/CXCR4 system are largely unknown. Recently, small non-coding RNAs, microRNAs (miRNAs) are involved in the metastatic process of several types of cancers. In this study, we examined the miRNA association involved in the mGluR5 expression using oral cancer cells, B88, which express functional CXCR4 and exhibit highly metastatic potentials. We examined the metastasis-related miRNAs in SDF-1 stimulated B88 cells by use of a miRNA microarray analysis. Consequently, we isolated miR-30 family which has predictive binding sites in 3’-UTR of mGluR5 mRNA in silico analysis. Among these miRNAs, we confirmed the downregulation of all miR-30 family in SDF-1 stimulated B88 cells by the real-time PCR analysis. Next, we transfected these miR-30 families in SDF-1 stimulated B88 cells. We confirmed the downregulation of mGluR5 by the miR-30a-5p and miR-30c-5p overexpression. These results indicated that SDF-1/CXCR4 system might regulate the metastases of oral cancer by the upregulation of mGluR5 via downregulation of miR-30 family. Citation Format: Nobuyuki Kuribayashi, Daisuke Uchida, Makoto Kinouchi, Chikako Koshiji, Sayaka Izumi, Kembun Hakata, Yuske Komiyama, Shuji Tsuchida, Tomonori Hasegawa, Hitoshi Kawamata. Regulation of metabotropic glutamate receptor 5 expression by the miR-30 downregulation induced by the SDF-1/CXCR4 system in oral cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1925.
Abstract LB-015: XIAP induction by the MAPK-eIF4G1 pathway drives NFκB activation in inflammatory breast cancer growth and therapeutic resistance
Authors: Myron K. Evans, Joseph Geradts, Courtney Edwards, Arianna Price, Arjun J. Arora, Amy J. Aldrich, Adrian Ramirez, Timothy J. Robinson, Peter B. Vermeulen, Steven van Laere, Gayathri R. Devi
Journal: Cancer Research (2016)

Abstract Inflammatory breast cancer (IBC) is the most lethal, distinct form of breast cancer, however, the basis for its aggressiveness and rapid acquisition of drug resistance is not fully understood. Using immunohistochemical analysis, we identified a strong correlation between high grade, high stage, and triple-negative status and elevated expression of the X-linked inhibitor of apoptosis protein (XIAP) in IBC. Molecular profiling of multiple IBC cell lines revealed that modulating XIAP expression can significantly alter the expression pattern of a 79-gene, characteristic IBC profile that was previously obtained from clinical samples. Using specific antagonists and RNAi, we determined that the mitogen activated protein kinase (MAPK) pathway and its interaction with the protein synthesis initiation factor eIF4G1, both of which are elevated in IBC, cooperate to drive XIAP induction and resistance to therapeutic apoptosis. Further, we found that XIAP expression directly correlates with activation of the transcription factor NFκB, a molecular component defining IBC. Mutational analysis revealed that the BIR1 domain of XIAP is essential for subsequent TAB1:IKKβ-dependent NFκB activation. After determining this association between XIAP and TAB1, we tested a peptide-mediated strategy used to block the BIR1:TAB1 interaction antagonized NFκB activity which led to decreased anchorage independent growth and reversed resistance to an EGFR tyrosine kinase inhibitor. Most significantly, orthotopic implantation of XIAP silenced IBC cells revealed the necessity of expression for IBC tumor growth, while overexpression of XIAP enhanced tumor growth. Our findings establish that XIAP augments the malignant properties in IBC by enhancing NFκB function, identify a druggable pathway with multiple targets, and provide feasibility for the development of novel therapeutics targeting the BIR1 domain of XIAP in IBC. Grant Support: Supported by American Cancer Society, the Duke Cancer Institute as part of the P30 Cancer Center Support Grant NIH CA014236, the Duke Department of Surgery, and DOD grant W81XWH-13-1-0047. Citation Format: Myron K. Evans, Joseph Geradts, Courtney Edwards, Arianna Price, Arjun J. Arora, Amy J. Aldrich, Adrian Ramirez, Timothy J. Robinson, Peter B. Vermeulen, Steven van Laere, Gayathri R. Devi. XIAP induction by the MAPK-eIF4G1 pathway drives NFκB activation in inflammatory breast cancer growth and therapeutic resistance. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-015.
RING domain–deficient BRCA1 promotes PARP inhibitor and platinum resistance
Authors: Yifan Wang, John J. Krais, Andrea J. Bernhardy, Emmanuelle Nicolas, Kathy Q. Cai, Maria I. Harrell, Hyoung H. Kim, Erin George, Elizabeth M. Swisher, Fiona Simpkins, Neil Johnson
Journal: Journal of Clinical Investigation (2016)

Patients with cancers that harbor breast cancer 1 (BRCA1) mutations initially respond well to platinum and poly(ADP-ribose) polymerase inhibitor (PARPi) therapy; however, resistance invariably arises in these patients and is a major clinical problem. The BRCA1185delAG allele is a common inherited mutation located close to the protein translation start site that is thought to produce a shortened, nonfunctional peptide. In this study, we investigated the mechanisms that lead to PARPi and platinum resistance in the SUM1315MO2 breast cancer cell line, which harbors a hemizygous BRCA1185delAG mutation. SUM1315MO2 cells were initially sensitive to PARPi and cisplatin but readily acquired resistance. PARPi- and cisplatin-resistant clones did not harbor secondary reversion mutations; rather, PARPi and platinum resistance required increased expression of a really interesting gene (RING) domain-deficient BRCA1 protein (Rdd-BRCA1). Initiation of translation occurred downstream of the frameshift mutation, probably at the BRCA1-Met-297 codon. In contrast to full-length BRCA1, Rdd-BRCA1 did not require BRCA1-associated RING domain 1 (BARD1) interaction for stability. Functionally, Rdd-BRCA1 formed irradiation-induced foci and supported RAD51 foci formation. Ectopic overexpression of Rdd-BRCA1 promoted partial PARPi and cisplatin resistance. Furthermore, Rdd-BRCA1 protein expression was detected in recurrent carcinomas from patients who carried germline BRCA1185delAG mutations. Taken together, these results indicate that RING-deficient BRCA1 proteins are hypomorphic and capable of contributing to PARPi and platinum resistance when expressed at high levels.