tbuckley/cabot-search huggingface dataset:
Marijuana use history in patients presenting with localized prostate cancer.
Authors: Romaine Charles Nichols, Christopher G Morris, Curtis Bryant, Bradford S. Hoppe, Randal H. Henderson, William M. Mendenhall, Nancy Price Mendenhall
Journal: Journal of Clinical Oncology (2019)

129 Background: Determine the incidence of past marijuana use in a large cohort of men diagnosed with localized prostate cancer to determine if marijuana use was correlated with: patient age; pretreatment T stage; Prostate specific antigen (PSA); Gleason Score; or clinical risk group. Methods: From August, 2006 to October 2018, 4305 patients received treatment for localized prostate cancer and are included in an outcomes tracking protocol. All patients were requested to complete a pre treatment information form which included the question: “Have you ever used marijuana?” 4277 (97%) answered the question either affirmatively or negatively. Responses were stratified by: patient birth year; clinical T stage, PSA level; highest Gleason score; and clinical risk group. Results: 3.8% of men born before 1940 reported marijuana use compared to 17.4% born between 1940 and 1950 and 38.6% born after 1950 (p&lt;0.0001). 19.8% of men with T1 tumors reported marijuana use compared to 18.1% of men with T2 tumors and 19.1% of men with T3 tumors (p=0.4494). 19.7% of men with a PSA less than 10 ng/ml reported marijuana use compared to 17.2% of men with a PSA between 10 and 20 ng/ml and 18.7% of men with a PSA over 20 ng/ml (p=0.4029). 20.8% of men with Gleason score of 6 or less reported marijuana use compared to 19.6% of men with a Gleason score of 7 and 13.5% with Gleason score of 8 or higher (p=0.0004). 20.8% of men with low risk presentation reported marijuana use compared to 19.9% of men with intermediate risk presentation and 14.1% of men with high risk presentation (p=0.0004). There was a significant positive association observed between increasing age and Gleason score (p&lt;0.0001). Conclusions: Men presenting with higher Gleason score tumors and higher risk disease were significantly less likely to report past marijuana use. It is likely that this finding is due to the greater incidence of high grade tumors seen in older patients.
Genetic Characteristics and Long-Term Outcomes of Korean Adult Patients with Ph-like Acute Lymphoblastic Leukemia Versus Non-Ph-like Acute Lymphoblastic Leukemia
Authors: Jae-Ho Yoon, Hanwool Cho, Seug Yun Yoon, Gi June Min, Sung-Soo Park, Silvia Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Myungshin Kim, Yonggoo Kim, Seok Lee
Journal: Blood (2018)
Targeting prostate cancer cells with neurotransmission modulating drugs.
Authors: Axel Hegele, Hendrik Heers, Anja Urbschat, Pietro Di Fazio, Eberhard Weihe, Ralf Kinscherf, Rainer Hofmann, Joerg Haenze
Journal: Journal of Clinical Oncology (2015)

e16093 Background: Innervation of prostate tissue by sympathetic and parasympathetic neurons is critical for prostate cancer (PCa) initiation and progression. Both, adrenergic and cholinergic receptor signaling contributes. Here, we aimed to analyze the expression and function of ß-adrenergic receptors and the secretory vesicle components SV2 and SNAP25 that interact with botulinum toxin type A (BoNT-A) in human prostate cancer cell lines Methods: ß2- and ß3-adrenergic receptor mRNA as wells as SV2 and SNAP25 mRNA were analyzed by quantitative realtime RT-PCR in human PC3, DU145, LNCaP and VCaP cells. Cellular responses towards isoproterenol (IsoP)or BoNT-A were measured by realtime cell analysis (Xcelligence). This system monitors changes in impedance (cell index) indicating proliferation or cytotoxicity. As pro-proliferative reference drug we included dihydrotestosterone and as cytotoxic drug docetaxel . Results: We detected mRNAs encoding ß2-adrenergic receptor, SV2 and SNAP25 in all cell lines. We selected DU145 and LNCaP cell line with relative high mRNA levels of these components for further functional analysis. We observed 1.6-fold increase of cell index upon addition of IsoP in DU145 but not in LNCaP cells. BoNT-A displayed no changes of cell index in both cell types. Conclusions: We conclude that IsoP can favor prostate cancer cell proliferation in certain PCa cells such as DU145 whereas BoNT-A does not reveal any intrinsic cytotoxic effects at least in the PCa cell lines studied.
Clinical and Histopathologic Characteristics of Melanocytic Lesions on the Volar Skin Without Typical Dermoscopic Patterns
Authors: Yasutomo Mikoshiba, Akane Minagawa, Hiroshi Koga, Yoshiharu Yokokawa, Hisashi Uhara, Ryuhei Okuyama
Journal: JAMA Dermatology (2019)

It is challenging to differentiate melanoma from melanocytic nevus on the volar skin in the absence of typical dermoscopic patterns.To identify the frequency and clinical and dermoscopic characteristics of melanocytic lesions on the volar skin not displaying a parallel furrow pattern, lattice-like pattern, fibrillar pattern, or parallel ridge pattern on results of dermoscopy.In this retrospective cohort study, a total of 504 melanocytic lesions on the volar skin were evaluated in the Shinshu University Hospital department of dermatology between January 1, 2000, and December 31, 2012. Dermoscopic images were independently assessed by 3 dermoscopists for the presence of established dermoscopic criteria. Statistical analysis was performed from October 1, 2017, to April 30, 2018.Frequency of dermoscopic criteria and corresponding clinical (patient age and size and location of lesion) and histopathologic features.Of 504 lesions, 110 (21.8%) (melanocytic nevus, 97; melanoma, 8; and equivocal melanocytic lesion, 5) from 108 patients (68 female and 40 male patients; mean age, 40.1 years [range, 1-86 years]) did not show a parallel furrow pattern, lattice-like pattern, fibrillar pattern, or parallel ridge pattern. Among them, the mean patient age was significantly higher for melanoma than for melanocytic nevus (65.3 vs 38.0 years; P < .001), as was mean maximum lesion diameter (11.8 vs 5.7 mm; P < .001). Melanomas and equivocal melanocytic lesions tended to be distributed on weight-bearing areas of the foot sole, such as the heel, while nevi were spread over non-weight-bearing regions. Dermoscopically, 95 melanocytic nevi (97.9%) were symmetrical in 1 or 2 axes while melanomas were not. A total of 91 melanocytic nevi (93.8%) had 1 or 2 colors per lesion, and 4 melanomas (50.0%) had more than 2 colors. Vascular structures were seen in 3 melanocytic nevi (3.1%) and 3 melanomas (37.5%). Blue-white structures were seen in 18 melanocytic nevi (18.6%) and 3 melanomas (37.5%). Dots and globules were seen in 22 melanocytic nevi (22.7%) and 4 melanomas (50.0%). Vascular structures, blue-white structures, and dots and globules were irregularly distributed in the melanomas. Ulcer, hyperkeratosis, and irregular streaks were observed only in melanomas.More than one-fifth of melanocytic lesions on the volar skin did not display typical dermoscopic patterns. Asymmetry, numerous colors (≥3), and other melanoma-specific dermoscopic findings were more frequently observed for melanomas. Clinical information, including patient age and lesion size and location, was helpful in differentiating melanoma from melanocytic nevus. Further prospective clinical studies are warranted to clarify the diagnostic accuracy of dermoscopy combined with clinical information.
Abstract 18191: Hispanic Ethnic Density and Cardiovascular Disease Mortality
Authors: Fatima Rodriguez, Hu Jiaqi, Katherine Hastings, Mark Cullen, Robert Harrington, Latha Palaniappan
Journal: Circulation (2017)

Background: Hispanics are the fastest growing ethnic group in the U.S., and little is known how Hispanic ethnic density impacts CVD mortality. Methods: We examined county-level deaths for Hispanics...
The in vitro cytotoxic and radiation sensitizing effects of docetaxel (Taxotere) and a novel taxane RPR116258 on Glioblastoma cell lines
Authors: Suzanne M. Hess, Amanda Mounce, Russel Sequeira, Joel G. Anderson, A. William Blackstock, Glenn J. Lesser
Journal: Cancer Research (2005)

1455  Current estimates suggest that at least 18,000 patients will be diagnosed with a primary malignant brain tumor in the United States in 2004. At least two thirds of these patients will die from their disease within one year; the majority with progressive glioblastoma multiforme (GBM), a highly aggressive, infiltrative malignant glioma. Standard treatment strategies for GBM include surgical resection or debulking followed by radiation therapy alone or in combination with chemotherapy. Despite this multi-modality approach, the median survival of all patients with GBM is only 9 to 12 months with negligible survival rates at 3 years. Because current therapeutic strategies are largely ineffective, novel strategies and therapies must be developed. We are interested in the efficacy of docetaxel and a novel oral taxane with blood-brain barrier permeability, RPR116258, as therapeutic agents in the treatment of GBM either as single agents or in combination with radiation. Taxanes function as anti-mitotic agents by promoting polymerization of microtubules and reducing depolymerization. Paclitaxel (Taxol) and docetaxel (Taxotere), the most widely studied taxanes, have activity against a wide range of solid tumors and paclitaxel has demonstrated radiation-sensitizing effects. We evaluated the cytotoxicity of docetaxel and RPR116258 using clonogenic survival assays in three GBM cell lines: SNB19, U251 and U138. A cell line specific effect was observed with IC50 values ranging from 0.2 to 2 nM. RPR116258 and docetaxel demonstrated similar cytotoxic efficacy in U251 and U138 cells, while SNB19 cells had a two fold lower IC50 value with RPR116258 (0.24 nM ± 0.03 SEM) than with docetaxel (0.49 nM ± 0.07 SEM). Both docetaxel and RPR116258 appeared to act as radiation sensitizing agents in all cell lines. At relevant doses of 2 Gy, surviving fractions in the taxane/XRT treated groups were 3-5 fold lower than the survival observed after radiation alone. Ongoing laboratory studies are focused on elucidating the mechanism of action of the observed radiation sensitization effect. Based on these observations and the ability of RPR116258 to partition across the blood-brain barrier, further in vivo experiments with drug and drug/radiation combinations in animals with intracranial tumor explants are planned.
Abstract P058: Cardiometabolic Risk Factors From a School-Based Cross-Sectional Screening Program
Authors: Lee A Pyles, Christa Lilly, Amy Joseph, Charles Mosimah, Eloise Elliott, William A Neal, Charles Mullett
Journal: Circulation (2019)

Introduction: Coronary Artery Risk Detection in Appalachian Communities is a school-based cross-sectional screening program to detect significant cardiometabolic disease risk factors (CMRFs) in WV children. Fifth graders have undergone school screening for family history, anthropometrics and lipid panel values since 1999 including screening for Acanthosis Nigricans (AN Pos or Neg). Our hypothesis is that presence of AN can predict need to screen for CMRFs. Methods: Parental consent and child assent were obtained before screening day using an IRB-approved protocol. Height and weight were used to calculate BMI and BMI%ile. Systolic blood pressure over 95%ile, triglyceride over 150 mg/dl, HDL under 40 mg/dl and BMI over 95%ile were tabulated and correlated. Glucose and HOMA IR were only checked for AN Pos subjects and thus not considered in analysis. Results: 102,930 5 th graders participated in CARDIAC up to 2017. 101,101 had BMI determination, 100,000 blood pressures, 67,710 lipid panels were checked. 27.9% of children (28715) were obese, defined as BMI over 95%ile and 18.4% (18,931 subjects) were overweight. 10.8% of AN pos children vs. 1.9% of all children exhibited 4 CMRFs (Obese BMI, Htn, high TG, low HDL, OR 7.31, 95% CL 6.4-8.35). Conclusion: AN correlated to CMRF clustering but many CMRF pos subjects were AN Neg (79.5% or 1236/1555 of those with 4 CMRFs). Multifactoral screening of lipids, BMI, blood pressure are indicated to identify risk for cardiovascular disease.
CHR Velocity as a predictor of early molecular response in patients with chronic myeloid leukemia.
Authors: Pankaj Malhotra, Santosh V Chikkodi, Shano Naseem, Alka Khadwal, Gaurav Prakash, Savita Kumari, Vikas Suri, Neelam Varma, Subhash Varma
Journal: Journal of Clinical Oncology (2015)

e18038 Background: Factors affecting early molecular response (EMR) in chronic myeloid leukemia (CML) have not been studied very well. We looked at the CHR velocity with other baseline factors for EMR in CML chronic phase (CP) patients put on imatinib mesylate (IM) based therapy. Methods: We prospectively studied newly diagnosed CML patients who were put on either generic IM (GIM) or Glivec. The diagnosis of CML was based on clinical examination, bone marrow and demonstration of BCR ABLIS transcripts by PCR. Physical examination and complete blood count were done weekly until CHR defined by standard criteria. CHR velocity was defined as number of weeks at which patient achieve CHR from the start of IM. The molecular responseIS was assessed at 3, 6 and 12 months by GeneXpert and co related with various factors. Results: The median age of 149 CML patients enrolled between 1st July 2013 - 31st October 2014 was 40 years (range 13-70 yrs) with male preponderance (61.1% males). Most patients presented with complaints of low-grade fever (51%) and abdominal fullness (30.2%). Spleen was palpable in 85.9% of patients. The median hemoglobin at presentation was 10.6gm/dl (range 4.8-18.4), white cell count 143.8x109/l(4.1- 697x109/l), platelet count of 304x109/l (5.3-1819x109/l). The median number of peripheral blood basophils and blasts were 3%. Most patients belonged to intermediate Sokal (47%) and Hasford (56.4%) risk. Out of 146 evaluable patients at 3 months, 96.6% (141) achieved CHR and 80.1% achieved BCR ABLIS of less than 10%. Out of 141 patients achieving CHR, 80 (56.7%) patients achieved CHR within 6-weeks and out of these 71 (89%) achieved BCR ABL of less than 10% at 3 months as opposed to 46 (75.4%) out of 61 who achieved CHR between 6-12 weeks (p = 0.037). Only one patients who had BCR ABLIS > 10% at 3 months achieved BCR ABLIS < 1% at 6 months or < 0.1% at 12 months(p < 0.001). Peripheral blasts < 5% and low-risk Sokal score were the only factors associated with achievement of BCR ABLIS < 10% at 3 months. No difference in terms of achieving CHR or EMR was found between GIM and Glivec. Conclusions: We define
Women’s triple-negative, first-line treatment: Improving outcomes in triple-negative breast cancer (TNBC) using molecular triaging and diagnostic imaging to guide neoadjuvant therapy (NACT).
Authors: Stacy L. Moulder, Naoto T. Ueno, Wei Tse Yang, Joe Ensor, Vicente Valero, Jennifer Keating Litton, Rashmi Krishna Murthy, Nuhad K. Ibrahim, Banu Arun, Elizabeth Ann Mittendorf, Kelly Hunt, Funda Meric-Bernstam, Alastair Mark Thompson, Helen Piwnica-Worms, Debu Tripathy, William Fraser Symmans
Journal: Journal of Clinical Oncology (2015)

TPS1113 Background: In TNBC, pathologic compete response (pCR/RCB-0) or minimal residual disease (RCB-I) to NACT is associated with a good prognosis while extensive residual disease (RCB-II-III) has a ~50% chance of recurrence. It is important to predict pCR, in order to direct responsive disease (RespD) toward standard NACT and non-responsive disease (NRD) to therapy on clinical trials. Methods: The use of genomic signatures (JAMA, 2011; 305:1873-81) and imaging to predict response to NACT will be validated and the impact of selecting pts for targeted therapy on clinical trial in predicted NRD will be determined. Pts will have primary tumor biopsy for molecular analyses and be randomized 2:1 to know results versus not (control). Pts will receive 4 cycles anthracycline-based NACT with imaging for response. Pts with molecular/imaging criteria for NRD will be offered a clinical trial based upon molecular profiling or based upon physician/patient choice (control). Pts having RespD in either arm receive taxane based NACT. INCLUSION: tumor size > 1.5 cm diameter; TNBC by standard assays; > 18 years of age; LVEF > 50%; adequate organ and bone marrow function. EXCLUSION: Stage IV disease; invasive cancer within 5 years; excisional biopsy of the primary; features that limit response assessment by imaging; unfit for taxane and/or antracycline regimens; prior anthracycline therapy; > grade II neuropathy; Zubrod performance status of > 2; history of serious cardiac events. Primary Aim: prospectively determine the impact of a molecular diagnostic/imaging platform in pts with localized invasive TNBC. Secondary Aims: compare rates of clinical trial enrollment, compare DFS, integrated biomarker analyses, identify therapeutic targets for resistant disease. A maximum of 360 pts will be randomized (2:1)using a group sequential design with one-sided O’Brien-Fleming boundaries, with two equally spaced binding interim tests for futility and superiority and one final test, having an overall Type I error .05 and power .80 to detect an improvement in pCR/RCB-I from 50% to 64%.
Long term follow up of organ preservation for advance laryngeal tumors treated with 75 mg/m<sup>2</sup> cisplatin based concurrent chemoradiation.
Authors: Hassan Iqbal, Raza Hussain, Arif Jamshed, Kamran Saeed, Sumayya Hameed, Sarah Jamshed
Journal: Journal of Clinical Oncology (2015)

e17086 Background: Organ preservation is the established treatment option for advance T stage laryngeal tumors. We report our experience of the reduced dose cisplatin (75mg/m2) based concurrent chemoradiation (CRT) in the treatment of advance laryngeal cancer. Methods: Between 2003 – 2009, a total of 101 patients with advance T3/T4 laryngeal tumors were treated with concurrent chemoradiation at Shaukat Khanum Memorial Cancer Hospital and Research Center. All patients were staged according to the AJCC classification (6th edition). Standard radiation dose to larynx was delivered at 70Gy in 35 fractions with 3 weekly cisplatin (75mg/m2). Induction chemotherapy (IC) was reserved for patients with bulky soft tissue disease. IC comprised of 2 drug regimen (cisplatin 75 mg/m2 and gemcitabine 1000 mg/m2). Tumors with extensive thyroid cartilage infiltration or strap muscle involvement were not included in this study since they were referred to upfront total laryngectomy. Results: Out of a total of 101 patients with follow up of 6 – 132 months (median 37), 90 (89%) were male and 65 (64%) smokers. Forty two patients received 3 weekly cycles of 2 drug induction chemotherapy regimen. The actual 5 and 10 year OS, RFS and DFS were: 53%, 48%, 50%, 47%, 49% and 46%. On univariate log rank test: nodal positivity (p-0.02), supraglottic site (p-0.01) and performance of tracheostomy at the start or during the coarse of treatment (p-0.008) were considered poor prognostic factors. G3-G4 toxicity for IC/CRT were anemia 1%/0%, neutropenia 17%/2%, vomiting 1%/2%, diarrhea 1%/0%, liver enzymes elevation 2%/1% and elevation of creatinine 2%/2% respectively.Twenty seven patients were sent for salvage laryngectomy secondary to recurrent/persistent disease or nonfunctional larynx. Conclusions: Organ preservation is certainly a proposed treatment option for advanced laryngeal tumors in developing countries with scare voice rehabilitation facilities and poor socioeconomic conditions. Our long term results of reduced cisplatin dose (75mg/m2) concurrent chemoradiation are comparable with acceptable toxicity.
Genomic analysis of mitochondrial mutations in chromophobe renal cell carcinoma by using low-depth whole genome sequencing.
Authors: Minyong Kang, Yong Ho Shin, Jae Young Joung, Seong Il Seo
Journal: Journal of Clinical Oncology (2019)

553 Background: Mitochondria have a circular genome that is independent of the nuclear genome of the nucleus. Mutations of mitochondrial DNA rarely occur during tumorigenesis. Chromophobe renal cell carcinoma (chRCCC) is a type of kidney tumor characterized by a morphologic abnormality of mitochondria. However, there is still little research on the existence of mitochondrial mutation in chRCC and how it plays a role in tumorigenesis. Here, we investigated the mutation patterns of mitochondria genome in chRCC using low-depth sequencing technique. Methods: We evaluated 17 patients with chRCC who underwent radical nephrectomy from December 2010 to January 2017. Mitochondrial genomic analysis was performed by low-depth sequencing. Varscan and MToolBox analysis programs were used to search for mutations. Germline mutation information reported in MtDB, Phylotree, and Mitomap databases was used to allocate patient haplogroups and exclude germline mutations. Results: Whole genome sequencing of 17 chRCC tissues at an average depth of 1x based on whole genome revealed that the mitochondrial genome was sequenced to an average of 630x. A total of 1,206 Haplotype frequency &gt; 0.25 mutations were found, of which 30 were mutations not reported in the database. Seven of them were identified as synonymous mutations (average of 0.41 and 41% per tumor), and three were truncating mutations (average of 0.18 per tumor; 18%). Truncating mutations were specifically identified as two frameshift indel and one stop gain mutation. Conclusions: In summary, our study showed that the frequency of truncating mutation of mitochondrial DNA was higher in chRCC compared to other solid tumors which have a low frequency of 1-2%. This finding suggests that dysfunctional mitochondria may play an oncogenic role in tumorigenesis of chRCC, while other tumors are predicted to undergo negative selection of mitochondrial truncating mutations during tumorigenesis. Based on these results, we are performing prospective study for evaluating mutational characteristics and associated morphological changes of mitochondria under electron microscopy.
Co-Administration of 3rdparty Partially HLA Matched Cytomegalovirus Specific T Cells with Initial Antiviral Pharmacotherapy for Post-Transplant Viral Reactivation
Authors: Emily Blyth, Leighton Edward Clancy, Elissa Atkins, GIllian Huang, David Collins, David Bishop, Kenneth P. Micklethwaite, David Gottlieb
Journal: Blood (2018)