tbuckley/cabot-search huggingface dataset:
Targeting the microtubule apparatus in indolent and mantle cell lymphoma with the novel epothilone anlog BMS 247550 induces major and durable remissions in very drug resistant disease
Authors: O. O’Connor, D. Straus, C. Moskowitz, P. Hamlin, C. Portlock, J. Gerecitano, E. Neylon, D. Colevas, A. Zelenetz
Journal: Journal of Clinical Oncology (2005)

6569 The epothilones are a new class of natural products that induce hyperstabilization of polymerized tubulin in a fashion similar to that known for the taxanes. Unique to these compounds is their ability to overcome acquired drug resistance, regardless of whether it is related to over expression of p-glycoprotein (MDR) or tubulin mutations. Given the novel mechanism, a Phase 2 study of BMS247550 in patients with drug resistant lymphoma was undertaken. A schedule of 25 mg/m2 weekly x 3 every 4 weeks was proposed based on established phase I data. All patients had to have objective evidence of disease progression prior to study entry. Patients were required to have: small lymphocytic lymphoma (SLL), CLL, follicular lymphoma (FL), marginal zone lymphoma or mantle cell lymphoma. Patients were eligible if they had no more than 4 prior lines of treatment. They were also required to meet the following criteria: measurable disease, KPS ≥ 60%, ANC ≥ 1000/μl, platelets ≥ 50,000/μl, total bilirubin ≤ 1.5 x upper limit of normal, AST/ALT < 2.5 x upper limit of normal and a creatinine of ≤ 2 x ULN. BMS 247550 is infused at a dose of 25 mg/m2 over one hour weekly for three every 4 weeks. A dose reduction to 20 mg/m2 was allowed for patients who developed any toxicity. Thus far, the major toxicities include modest grade 2 myelosuppression that is cumulative in nature, reversible grade 2 sensory neuropathy, and asthenia. To date, 11 patients have been treated, one of whom is inevaluable secondary to disease progression. One of two patients with SLL achieved a partial remission lasting over 9 months; one of two patients with FL achieved a remission lasting over 7 months. While the study is still accruing, four of five evaluable patients with MCL have achieved major dramatic remission, including one very good PR, and one PR. Two other patients have had clinical regression of their disease after one or two doses. This is the first paper to demonstrate marked activity of this class of molecules in patients with lymphoma. An update of these data will be presented with additional patients and longer follow-up. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Controversies in neuro-oncology: role of whole-brain radiation therapy in the treatment of newly diagnosed brain metastases
Authors: Patrick Y. Wen
Journal: Neuro-Oncology (2015)

As therapies for systemic cancers improve and patients survive longer, the incidence of brain metastases is increasing. Current therapies include varying combinations of surgery, stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), and in a small subset of patients, systemic therapy. The use of SRS to treat brain metastases has been one of the major successes in neuro-oncology, providing effective local control of even radioresistant brain metastases. Several studies have compared the outcomes of patients with a limited number of brain metastases treated with surgery or radiosurgery alone, with the addition of WBRT. – 4 These studies, which usually included heterogeneous tumor histologies and varying extent of systemic disease, have generally shown improved intracranial control with the addition of WBRT, but no significant improvement in overall survival, and an increased risk of neurocognitive impairment. Most recently, at the 2015 American Society of Clinical Oncology annual meeting, Brown et al presented the results of the North Central Cancer Treatment Group (NCCTG) (Alliance) N0574 study, a phase III trial comparing SRS+WBRT to SRS alone in patients with 1–3 brain metastases. This study for the first time used decline in cognitive function at 3 months as the primary endpoint. Cognitive deterioration at 3 months was significantly more frequent in the WBRT+SRS group than the SRS alone group, involving especially immediate recall, memory, and verbal fluency. As with prior studies, intracranial disease control was improved with WBRT but there was no improvement in overall survival. This study adds to the growing body of literature addressing this issue. Nonetheless, there is currently no consensus on the value of WBRT and the optimal management of patients with brain metastases remains a dilemma that confronts clinicians looking after these patients. In this issue of Neuro-Oncology, Dr Arjun Sahgal from the University of Toronto discusses the data in favor of omitting WBRT from patients with newly-diagnosed brain metastases, while Dr. Minesh Mehta from the University of Maryland provides the counter-argument of including WBRT for these patients.
P53 Functional Assessment and Correlation With 17p Deletion and/Or TP53 Mutation Status In Chronic Lymphocytic Leukemia (CLL). A Preliminary Report Of The ICLL001 Bomp Trial On Behalf Of The French CLL Intergroup (GCFLLC/MW - GOELAMS)
Authors: Magali Le Garff-Tavernier, Lauren Veronese, Florence Nguyen-Khac, Marie-Sarah Dilhuydy, Patricia Combes, Véronique Leblond, Pierre Feugier, Beatrice Mahe, Laurence Sanhès, Alain Delmer, Loic Ysebaert, Aurore Grelier, Malgorzata Truchan-Graczyk, Brigitte Dreyfus, Emmanuelle Ferrant, Stéphane Leprêtre, Frederic Davi, Bruno Pereira, Roselyne Delepine, Romain Guièze, Jacques-Olivier Bay, Helene Merle-Beral, Sophie De Guibert, Olivier Tournilhac
Journal: Blood (2013)
Prolonged postprocedural outbreak of Mycobacterium massiliense infections associated with ultrasound transmission gel
Authors: A. Cheng, W.-H. Sheng, Y.-C. Huang, H.-Y. Sun, Y.-T. Tsai, M.-L. Chen, Y.-C. Liu, Y.-C. Chuang, S.-C. Huang, C.-I. Chang, L.-Y. Chang, W.-C. Huang, P.-R. Hsueh, C.-C. Hung, Y.-C. Chen, S.-C. Chang
Journal: Clinical Microbiology and Infection (2016)
Bystander vaccine therapy in mantle cell lymphoma (MCL): Phase II clinical results.
Authors: B. D. Shah, J. Tao, L. Sokol, P. A. Chervenick, M. R. Tomblyn, J. Pinilla-Ibarz, L. Moscinski, S. Antonia, E. M. Sotomayor, S. Dessureault
Journal: Journal of Clinical Oncology (2010)

2608 Background: A phase I study showed that vaccination of cancer patients with irradiated autologous tumor cells and GM.CD40L bystander cells (engineered to secrete GM-CSF and express CD40L) is safe, recruits/activates dendritic cells, and elicits tumor- specific T-cell responses. We tested this vaccine strategy in patients with MCL, an aggressive and incurable B-cell malignancy. Methods: After lymph node resection (for autologous tumor harvest), 4-6 cycles of chemotherapy, and restaging (CT, endoscopy, bone marrow biopsy), patients with usable vaccine who achieved a PR or CR lasting 1 month were vaccinated x4 at 28-day intervals and received IL-2 (0.5 × 106 U SC BID × 14 d). Patients were monitored for toxicity, tumor response, tumor-specific immune responses, and PFS/OS. Results: 43 were enrolled, including 21 with relapsed MCL, 20 with int/high MIPI, and 6 with blastoid MCL. Twenty never received vaccine: 2 withdrew consent, 1 progressed rapidly prior to lymph node harvest, 7 had insufficient or contaminated specimens, and 10 progressed/died during chemotherapy. The unvaccinated were older (68.4y vs. 62.8y; p=0.026) but otherwise did not differ significantly by stage, LDH, MIPI, de novo status, or number of prior treatments. Among 23 treated, 10 had relapsed disease (median 3.6 prior regimens), 10 had an int/high MIPI, and 2 had blastoid MCL. Pre-vaccination response following chemotherapy included 7 CR and 16 PR. At 6 months after vaccination, 2 pts in PR converted to CR, 10 progressed (including 3 who progressed after only 1-2 vaccines), and 11 had no change. Patients receiving at least one vaccine constitute the analyzed population. Accordingly, median PFS and OS are calculated from receipt of first vaccine. Despite a short median PFS (9 mo), this high-risk cohort demonstrated an unexpectedly prolonged median OS, which has not been reached after a median follow-up of 30 mo (range 8-68 mo). Conclusions: Reminiscent of our phase I data, our vaccination approach for MCL seems to abrogate the aggressiveness of this disease resulting in an unexpected prolongation of OS. No significant financial relationships to disclose.
Sentinel and axillary nodes of the breast distinguished from those of the arm by 3D-CT lymphography and selectively dissected by endoscopic surgery
Authors: K. Yamashita, S. Haga, K. Shimizu
Journal: Journal of Clinical Oncology (2009)

616 Background: In early breast cancer, the presence of metastasis in axillary lymph nodes (AN) is an important factor in prognosis and further treatment. However, AN dissection causes many complications such as contracture of shoulder joint, lymph edema, and paralysis of upper extremities. Sentinel node (SN) biopsy provides us valuable information about no need to dissect AN for node-negative patients. However, on node-positive patients, the conventional AN dissection has been performed. 3D-CT lymphography (LG) can show the precise individual lymphatic flow not only from the breast tumor to SN but also from SN to venous angle, which means breast lymphatic channel. We applied 3D-CT LG to distinguish them from the arm channel to avoid any arm complications. Methods: 3D-CT LG was performed on the day before surgery to mark SN on the skin. Above the tumor and near the areola and the arm pit, 2 ml of Iopamidol 300 was injected subcutaneously. Images of 16-channel multidetector-row helical CT scan were taken at 1, 3, and 5 min after injection. They were reconstructed to produce a 3D image of lymph ducts and lymph nodes. SN biopsy and AN sampling were performed by dye-staining method using endoscopy. Results:We performed SN biopsy with 3D-CT LG on 160 patients. 3D-CT LG clearly showed the precise lymphatic flow from the tumor to SN. It can show SN at only one min after injection. But following up to 5 min, we can follow the lymph ducts beyond SN into the second to the fifth node groups toward the venous angle with complex plexus, observed in the surrounding anatomical architecture. Detection rate was 100% for SN; 80% for the third group; and 30% for the fifth group. The arm lymph flow was distinguished by the connections between the breast and the arm flow, observed 39% and 71% in the fourth and the fifth group. SN was shared from between the breast and the arm in 5 patients (3.1%). They complained arm edema only by SN biopsy. We can distinguish and sample AN drained from the breast, guided by 3D-CT LG and dye-staining using endoscopy. Conclusions:By 3D-CT LG, we can recognize the accurate and more precise lymph flow in the surrounding anatomical architecture. It helps us easily to pursuit lymph flow and to remove SN and AN from the breast selectively using endoscopic surgery. No significant financial relationships to disclose.
The significance of urine NMP22 in the screening of urothelial cancer (comparison of ELISA and immunochromatography method)
Authors: H. Ikeda, Y. Ishida, T. Dejima, M. Nomura, H. Sanefuji
Journal: Journal of Clinical Oncology (2009)

e16024 Background: The early diagnosis of urothelial cancer allows for effective local treatment and optimizes the success of surgical therapy. Urine nuclear matrix protein 22 (NMP22) was introduced for the detection of transitional cell carcinoma. Add to old NMP22 (ELISA), new NMP22 (immunochromotography method : BladderChek) can be available from 2004. The objective of this study is to determine whether there are any correlation between urine NMP22 (two methods) and the grade or stage of urothelial cancer, and whether it can serve as a biochemical marker of urothelial cancer. Methods: A total of 246 patients with hematuria or followed up after TUR-BT, from March 2007 to December 2007,visited our hospital and subsequently underwent cystoscopy. The 246 patients provided voided urine samples. We immediately examined urine cytology and NMP22 (two methods). We set the cut off value on 12.0U/ml for NMP22 (ELISA). NMP22 (BladderChek) was judged by qualitative analysis. We decided that in urine cytology, classI,II,III were negative, while IV,V were positive by Papanicolaou classification. Results: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were 66.7 %, 98.3 %, 81.8 %, 96.3 % in urine cytology, 40.7 %, 75.9 %, 16.2 %, 91.8 % in NMP22 (ELISA), 59.3 %, 79.3 %, 24.6 %, 94.5 % in NMP22 (BladderChek). In 9 cases with false negative of urine cytology, 4 cases were picked up by NMP22 (ELISA), and 5 cases by NMP22 (BladderChek). Sensitivity of grade 1 was 33.3 % in urine cytology, while 66.7 % in NMP22 (BladderChek). By adding NMP22 (BladderChek) to urine cytology, sensitivity rose about 18 %. Conclusions: The sensitivity of urine cytology was unexpectedly high. NMP22 (BladderChek) is more useful than NMP22 (ELISA) because of higher sensitivity, specificity and advantage of simplicity, rapidity. It seems that the addition of NMP22 (BladderChek) to urine cytology is beneficial. No significant financial relationships to disclose.
Results of intraarterial cisplatin and hyperfractionated radiotherapy in locally advanced cancer of the oropharynx and oral cavity
Authors: S. M. Arnold, W. W. Graham, J. Valentino, Y. Brill, W. Regine, P. Spring, C. Given, M. Mohiuddin, W. St Claire, M. Kudrimoti
Journal: Journal of Clinical Oncology (2006)

5563 Background: Intraarterial cisplatin and hyperfractionated radiation (HYPERADPLAT) is an accepted therapy for Stage III and IV head and neck cancer. We present long-term follow-up of patients with OP and OC cancer treated with HYPERADPLAT at a single institution. Methods: 44 patients with Stage III-IV squamous cell carcinomas of the OP or OC were treated with the HYPERRADPLAT regimen consisting of external beam radiotherapy (76.8–81.6 Gy) delivered in 1.2 Gy BID fractions with intraarterial cisplatin (150 mg/m 2 ) administered when patients had reached 60 Gy. Tumor response, disease free survival (DFS), overall survival (OS), and toxicity were assessed for all patients according to NCI CCT criteria. Results: Of 44 patients, 21 had tumors of the base of tongue, 14-tonsil, 4-floor of mouth, and 5-other. Eighty eight percent of patients had T4 tumors and 7% had T3 tumors. Complete tumor response was observed in 86% of patients and 14% had a partial response. Lymph node metastases were present in 84% of patients with 78% of node positive patients having a complete nodal response and 19% with a partial response to treatment. Three-year DFS was 55% and OS was 45%. Locoregional recurrence was noted in 30% of patients and 16% had distant failure. Overall recurrence was noted in 47% of patients with a median time to recurrence of 8 months (range 4–55 months). Median weight loss during treatment was 9% of initial body weight and 28 patients required a feeding tube within 6 months of starting treatment. Grade 3 mucositis was noted in 68% of patients and 3 patients developed Grade 4 toxicity (2 mucosal, 1 hematologic). Conclusions: HYPERRADPLAT results in excellent tumor control that is well tolerated with minimal Grade 4 toxicity in patients with advanced poor prognosis cancers of the OP and OC. These results compare favorably with historically reported control rates and response for patients with a significantly high percentage of T4 tumors of the oropharynx and oral cavity. No significant financial relationships to disclose.
Abstract 680: HMGB1 regulates autophagy and apoptosis to promote chemotherapy resistance in multiple myeloma
Authors: Xingding Zhang, Lin Qi, Lin Yang
Journal: Cancer Research (2014)

Abstract Multiple myeloma is the second most frequently diagnosed hematologic malignancy in the United States after non-Hodgkin lymphoma. Unfortunately, multiple myeloma remains incurable, and virtually all patients eventually relapse with disease that is typically more resistant to therapy than in prior lines of treatment, for which the underlying molecular mechanisms remain unclear. In this study, we showed that high-mobility group box 1 (HMGB1), the best characterized damage-associated molecular pattern, in the development of chemotherapy resistance in multiple myeloma. To examine its potential role of chemotherapy resistance in myeloma, we detected protein expression of HMGB1 treated with anticancer chemotherapy agent doxorubicin and observed that HMGB1 was upregulated by different concentrations of doxorubicin in myeloma cells. Chemosensitivity assay was performed with RPMI 8226 and U266 cells with knockdown/overexpression of HMGB1 and treated with doxorubicin, and cells were detected for their viability by WST-1 assay after 72 hr. Consistently, shRNA interference-mediated knockdown of HMGB1 cells exhibited significant sensitized to doxorubicin treatment compared to non-targeting shRNA cells, and HMGB1-overexpressing cells significantly resistance to doxorubicin. Furthermore, studies in xenograft models showed that shRNA of HMGB1 also sensitized the chemosensitivity of multiple myeloma cells in vivo. At the molecular level, mechanistic investigation showed that shRNA of HMGB1 decreased autophagy, which is an intracellular self-defense mechanism to drug resistance, by inhibition of the autophagic marker microtubule-associated protein light chain 3-II and increasing of sequestosome 1 (p62) and autophagosome formation. Finally, we found that HMGB1 regulated autophagy and apoptosis by binding to p53 and Beclin1, and p53 is a negative regulator of the HMGB1/Beclin1 complex. Taken together, these data support the hypothesis that HMGB1 modulates chemotherapy resistance in myeloma through effects on the pathway of autophagy and apoptosis, as well as a target for strategies to aim at laying the foundation for further clinical studies, and overcome chemoresistance in multiple myeloma. Note: This abstract was not presented at the meeting. Citation Format: Xingding Zhang, Lin Qi, Lin Yang. HMGB1 regulates autophagy and apoptosis to promote chemotherapy resistance in multiple myeloma. [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 680. doi:10.1158/1538-7445.AM2014-680
Green tea’s effect on anti-estrogen treatment
Authors: Maryam R. Sartippour, Richard Pietras, David Heber, Zhang Liping, Ming Lu, Mai N. Brooks
Journal: Cancer Research (2006)

2251  We observed that green tea increases the inhibitory effect of tamoxifen on the proliferation of multiple ER (estrogen receptor-α)-positive human breast cancer cells in vitro. The ID50 (inhibitory dose 50) for tamoxifen alone were as follows: 10.2 μM for MCF-7, 7.2 μM for ZR-75, and 8.4 μM for T47-D. We then demonstrated that the addition of 5 μg/ml of green tea extract decreased the ID50 of tamoxifen to 200 nM for MCF-7, 36 nM for ZR-75 and 30 nM for T47-D. It thus appears that green tea can add to tamoxifen’s effectiveness on ER-positive breast cancer cells. Further experiments showed that green tea did not affect substrate binding to the estrogen receptor. However, green tea decreased the level of estrogen receptors, blocked ER-dependent transcription, as well as estradiol-induced phosphorylation and nuclear localization of mitogen activated protein kinase (MAPK). The addition of green tea to tamoxifen potentiated these ER-dependent activities. These results suggest that consumption of green tea during tamoxifen treatment may be beneficial for breast cancer patients.
Is mammography adequate for screening BRCA mutation carriers with low breast density?
Authors: R. Bigenwald, E. Warner, A. Gunasekara, K. Hill, P. Causer, S. Messner, A. Eisen, D. Plewes, S. Narod, M. Yaffe
Journal: Journal of Clinical Oncology (2006)

10014 Background: Several large observational studies have demonstrated that magnetic resonance imaging (MRI) is much more sensitive than M (sensitivity 71–96% vs. 28–43%) for screening women &gt; age 25 at high risk for hereditary breast cancer. However, MRI is much more costly and less specific than M. The extent to which the low sensitivity of M in these studies is due to the greater average breast density of younger women is unknown. Accordingly, we sought to determine the sensitivity of M and MRI according to breast density for the detection of breast cancer in a screening study of BRCA mutation carriers. Methods: Breast density was measured on the screening mammogram of the contralateral breast for all women who developed in-situ or invasive breast cancer on study. Density was measured in 2 ways: qualitatively according to the four categories characterized by the BIRADS system: 1) mostly fatty, 2) scattered fibroglandular tissue, 3) heterogeneously dense, 4) extremely dense; and semi-quantitatively using computer-aided techniques with subsequent classification as: A) ≤10%, B) 11–25%, C) 26%-50%, or D) &gt;50% density. Results: Between 11/97 and 06/05 a total of 39 cases (12 in-situ and 27 invasive) were found in 36 mutation carriers (19 BRCA1 and 17 BRCA2). Mean age of the women with cancer was 48 (range 34 to 64). Average semi-quantitative breast density for BRCA1 mutation carriers was 28% and for BRCA2 was 27%. Sensitivity of M vs. MRI for in-situ cases was 25% vs. 83%, and for invasive cases was 30% vs. 93%. Sensitivities for BRCA1 and BRCA2 mutation carriers were similar. For BIRADS 1 to 4 respectively M detected 1/3 (33%), 5/11 (45%), 4/22 (18%), and 1/3 (33%) of cases; and for density groups A to D respectively detected 2/6 (33%), 7/15 (47%), 1/11 (9%) and, 1/7 (14%). Conclusion: Although there was a trend towards decreasing mammographic sensitivity with increasing density, even among BRCA mutation carriers with low breast density mammography is an inadequate screening tool. No significant financial relationships to disclose.
Selective Inhibition of Membrane Type 1 Matrix Metalloproteinase Abrogates Progression of Experimental Inflammatory Arthritis: Synergy With Tumor Necrosis Factor Blockade
Authors: Kazuyo Kaneko, Richard O. Williams, Daniel T. Dransfield, Andrew E. Nixon, Ann Sandison, Yoshifumi Itoh
Journal: Arthritis & Rheumatology (2015)

Objective In rheumatoid arthritis (RA), destruction of articular cartilage by the inflamed synovium is considered to be driven by increased activities of proteolytic enzymes, including matrix metalloproteinases (MMPs). The purpose of this study was to investigate the therapeutic potential of selective inhibition of membrane type 1 MMP (MT1‐MMP) and its combination with tumor necrosis factor (TNF) blockage in mice with collagen‐induced arthritis (CIA). Methods CIA was induced in DBA/1 mice by immunization with bovine type II collagen. From the onset of clinical arthritis, mice were treated with MT1‐MMP selective inhibitory antibody DX‐2400 and/or TNFR‐Fc fusion protein. Disease progression was monitored daily, and serum, lymph nodes, and affected paws were collected at the end of the study for cytokine and histologic analyses. For in vitro analysis, bone marrow–derived macrophages were stimulated with lipopolysaccharide for 24 hours in the presence of DX‐2400 and/or TNFR‐Fc to analyze cytokine production and phenotype. Results DX‐2400 treatment significantly reduced cartilage degradation and disease progression in mice with CIA. Importantly, when combined with TNF blockade, DX‐2400 acted synergistically, inducing long‐term benefit. DX‐2400 also inhibited the up‐regulation of interleukin‐12 (IL‐12)/IL‐23 p40 via polarization toward an M2 phenotype in bone marrow–derived macrophages. Increased production of IL‐17 induced by anti‐TNF, which correlated with an incomplete response to anti‐TNF, was abrogated by combined treatment with DX‐2400 in CIA. Conclusion Targeting MT1‐MMP provides a potential strategy for joint protection, and its combination with TNF blockade may be particularly beneficial in RA patients with an inadequate response to anti‐TNF therapy.