tbuckley/cabot-search huggingface dataset:
Differences in the Tumor-Associated Reactivity of Blood Lymphocytes and Tumor-Draining Lymph Node Cells in Sarcoma Patients 2
Authors: Farkas Vánky, Jan Stjernswärd, Ulf Nilsonne, Rolf Sundblad
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Differences in the Tumor-Associated Reactivity of Blood Lymphocytes and Tumor-Draining Lymph Node Cells in Sarcoma Patients Get access Farkas Vánky, Farkas Vánky Department of Tumor Biology, Karolinska Institutet; Radiumhemmet, Department of Orthopedic Surgery, and Department of Surgery, Karolinska Sjukhuset, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Jan Stjernswärd, Jan Stjernswärd Department of Tumor Biology, Karolinska Institutet; Radiumhemmet, Department of Orthopedic Surgery, and Department of Surgery, Karolinska Sjukhuset, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Ulf Nilsonne, Ulf Nilsonne Department of Tumor Biology, Karolinska Institutet; Radiumhemmet, Department of Orthopedic Surgery, and Department of Surgery, Karolinska Sjukhuset, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Rolf Sundblad Rolf Sundblad Department of Tumor Biology, Karolinska Institutet; Radiumhemmet, Department of Orthopedic Surgery, and Department of Surgery, Karolinska Sjukhuset, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 17–24, https://doi.org/10.1093/jnci/51.1.17 Published: 01 July 1973 Article history Received: 05 December 1972 Accepted: 07 March 1973 Published: 01 July 1973
Safety and tolerability of lapatinib ditosylate given concurrently with docetaxel, carboplatin, and trastuzumab (TCHL) as part of adjuvant therapy for patients with HER2+ breast cancer: Pilot data from the North Central Cancer Treatment Group Trial N083E.
Authors: C. Bueno Hume, A. Moreno-Aspitia, D. W. Hillman, A. T. Perez, B. Chen, R. B. Jenkins, A. C. Dueck, D. B. Johnson, R. L. Carolla, E. A. Perez
Journal: Journal of Clinical Oncology (2010)

565 Background: The nonanthracycline regimen of docetaxel (T), carboplatin (C), and trastuzumab (H) is available for patients with early HER2+ breast cancer. We sought to evaluate the tolerability of adding L to adjuvant TCH, in anticipation of allowing such regimen in the ALTTO adjuvant study. Methods: A single-arm phase II safety study of T (75 mg/m2 d1), C (AUC 6 d1), H (4 mg/kg loading dose, then 2 mg/kg d1, d8, d15), and L (1,000 mg PO qd) q 21d × 6 cycles, followed by H (6 mg/kg, q 21d × 12) and L (1,000 mg PO qd × 34 weeks) for a total of 52 weeks of treatment was conducted. Filgrastrim or pegfilgrastrim was administered as part of cycles 1-6. Primary endpoint was cardiac safety and overall tolerability. Results: The study completed accrual of 30 pts from March to November 2009. We report safety data available for the first 24 pts. Median follow up of 2.7 months. Median pt age 51.8 (range 29-70). Mean baseline LVEF was 62.6%; at end of cycle 6 was 60% for the first 9 evaluable pts who have completed cycle 1-6. No pts experienced CHF or cardiac death. G3 diarrhea occurred in 8 pts (33%), all cases during cycle 1. Four of them required dose modification, with 3 pts able to tolerate subsequent cycles with resolution of the diarrhea. Other G3/4 AEs with incidence > 5% include neutropenia (N = 6, 25%), nausea (N = 3, 13%), thrombocytopenia (N = 3, 13%), hypersensitivity (N = 3, 13%), and hypokalemia (N=2, 8%). Four pts came off study due to AEs (1 each, diarrhea, hypersensitivity, rash, bone pain/fatigue/leukopenia) and 1 pt withdrew after 2 days of treatment with L. Conclusions: No cardiac safety signal noted so far with TCHL but continued monitoring is needed to assess long term cardiac effects. Diarrhea is a frequent adverse event with TCHL, using an L dose of 1,000 mg/day. Updated 6-month data on all 30 pts will be available by ASCO 2010. Based on the results of the current trial, the ALTTO treatment design 2 has been amended to allow the TCHL regimen to be part of the treatment options (but using an L dose of 750 mg/day). Support was provided by the NCI (CA25224), Breast Cancer Research Foundation, and GlaxoSmithKline. No significant financial relationships to disclose.
Relationship of Cutaneous Malignant Melanoma to Individual Sunlight-Exposure Habits&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: C D Holman, B K Armstrong, P J Heenan
Journal: JNCI Journal of the National Cancer Institute (1986)

The relationships of different histologic types of cutaneous malignant melanoma to occupational and recreational sunlight exposure, habits of clothing, sunburn histories, and use of sunscreening agents were examined in a case-control study of 507 patients and 507 matched controls in Western Australia. Variations in relationships according to the primary site of melanoma were also examined. An increased incidence rate of superficial spreading melanoma was associated with low total outdoor exposure in early adulthood and frequent participation in boating and fishing. Superficial spreading melanoma of the trunk was also related to frequency of sunbathing at ages 15–24 years and of exposure of the trunk while working outdoors. In women the rate ratio for all types of melanoma occurring on the trunk was estimated at 13.0 (95% confidence interval, 2.0–83.9) in those who wore a bikini or bathed nude at ages 15–24 years compared with those wearing a conservative one-piece bathing suit. There was little evidence that sunbathing or wearing a bikini within 10 years of case diagnosis were risk factors for melanoma of the trunk. After control of confounding due to constitutional factors, only Hutchinson's melanotic freckle melanoma showed a relationship to severe sunburn. For nodular melanoma, sunburn appeared to be protective. Although many of the results supported the hypothesis that melanomas other than the Hutchinson's melanotic freckle type are related to occasional bursts of recreational sun exposure during a susceptible period in early adult life, little support for the hypothesis was obtained when recreational sun exposure was expressed as a proportion of total outdoor exposure, which had been considered a priori to be an index of intermittent sunlight exposure.
Randomized Pii of Concurrent Vs Sequential Alternating Gefitinib and Chemotherapy in Egfr-Mutant Nsclc: Nej005/Tcog0902
Authors: Koichi Minato, Satoshi Oizumi, Shunichi Sugawara, Toshiyuki Harada, Akira Inoue, Yuka Fujita, Makoto Maemondo, Hirohisa Yoshizawa, Minoru Kurihara, Toshihiro Nukiwa
Journal: Annals of Oncology (2014)
UV Radiation-Induced Tumors in Haired Mice: Identification as Squamous Cell Carcinomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: W L Morison, M S Jerdan, T L Hoover, E R Farmer
Journal: JNCI Journal of the National Cancer Institute (1986)

The most common tumor induced by UV radiation in haired mice is considered to be a fibrosarcoma on the basis of its presentation as a nodule in the skin and on the basis of a spindled appearance upon light microscopic examination. A squamous cell carcinoma is thought to be a much less common tumor. In the present report this concept was reevaluated in mammary tumor virus-free C3H/HeNCr (C3H-) mice. From first appearance, almost all lesions upon gross morphologic examination have an epidermal component and initially are similar to solar keratoses in humans. The lesions then become nodular and eventually develop central ulceration, often with a rolled border characteristic of squamous cell carcinomas. The morphology upon light microscopic examination ranged from well-differentiated squamous cell carcinoma to a poorly differentiated spindle cell neoplasm. Occasionally, variable patterns of squamous differentiation were seen in the same lesion. Immunoperoxidase examination with a polyclonal antikeratin serum demonstrated the presence of keratin in 84 of 87 tumors. Frequent, poorly formed desmosomes were found on ultrastructural examination. These tumors usually had a regressor phenotype upon transplantation into recipients. In conclusion, almost all UV radiation-induced tumors in C3H- mice are squamous cell carcinomas, and these tumors are usually antigenic.
Dermoscopic clues to differentiate facial lentigo maligna from pigmented actinic keratosis
Authors: A. Lallas, P. Tschandl, A. Kyrgidis, W. Stolz, H. Rabinovitz, A. Cameron, J.Y. Gourhant, J. Giacomel, H. Kittler, J. Muir, G. Argenziano, R. Hofmann-Wellenhof, I. Zalaudek
Journal: British Journal of Dermatology (2015)

Dermoscopy is limited in differentiating accurately between pigmented lentigo maligna (LM) and pigmented actinic keratosis (PAK). This might be related to the fact that most studies have focused on pigmented criteria only, without considering additional recognizable features.To investigate the diagnostic accuracy of established dermoscopic criteria for pigmented LM and PAK, but including in the evaluation features previously associated with nonpigmented facial actinic keratosis.Retrospectively enrolled cases of histopathologically diagnosed LM, PAK and solar lentigo/early seborrhoeic keratosis (SL/SK) were dermoscopically evaluated for the presence of predefined criteria. Univariate and multivariate regression analyses were performed and receiver operating characteristic curves were used.The study sample consisted of 70 LMs, 56 PAKs and 18 SL/SKs. In a multivariate analysis, the most potent predictors of LM were grey rhomboids (sixfold increased probability of LM), nonevident follicles (fourfold) and intense pigmentation (twofold). In contrast, white circles, scales and red colour were significantly correlated with PAK, posing a 14-fold, eightfold and fourfold probability for PAK, respectively. The absence of evident follicles also represented a frequent LM criterion, characterizing 71% of LMs.White and evident follicles, scales and red colour represent significant diagnostic clues for PAK. Conversely, intense pigmentation and grey rhomboidal lines appear highly suggestive of LM.
Phase I study to determine tolerability and pharmacokinetics (PK) of SB-743921, a novel kinesin spindle protein (KSP) inhibitor
Authors: K. D. Holen, C. P. Belani, G. Wilding, S. Ramalingam, J. L. Heideman, R. K. Ramanathan, C. J. Bowen, D. D. Williams, J. P. Hodge, M. M. Dar
Journal: Journal of Clinical Oncology (2006)

2000 Background: SB-743921, a potent and selective inhibitor of KSP (K i =100 pM; &gt;40,000-fold selectivity vs other kinesins), causes mitotic arrest, potent inhibition of tumor cell proliferation, and demonstrates activity in a broad range of human tumor xenografts. Methods: A phase I study was conducted to determine the maximum tolerated dose (MTD) and PK profile of SB-743921 when administered IV over 60 minutes every 21 (Q 21) days (d). Results: 44 patients (pts) (M/F 19/25), median age 61.5 yrs (range 32–80, with solid tumors were treated at doses of 2 (n=2), 4 (n=27), 5 (n=6), 6 (n=3), and 8 (n=6) mg/m 2 (median cycles 2, range 1–10, total cycles 101). Frequent tumor types included colorectal (n=11), ovarian (n=5), NSCLC (n=5), esophageal (n=4), and pancreatic (n=4). Dose-limiting toxicities (DLTs) at 8 mg/m 2 consisted of (max CTC grade/pt) prolonged grade (gr) 4 neutropenia (n=2), gr 3 elevated ALT/AST (n=1), and gr 3 elevated bilirubin (n=1). DLTs at 6 mg/m 2 were gr 3 hyponatremia (n=1) and prolonged gr 4 neutropenia (n=1). DLTs at 5 mg/m 2 were limited to febrile neutropenia (n=2). The 4 mg/m 2 dose level was determined as the phase II dose. Toxicities at 4 mg/m 2 included gr 1 fatigue (n=8) and neutropenia [gr 1 (n=4), gr 2 (n=7), gr 3 (n=3), gr 4 (n=2)]. Neutropenia nadir was day 6–8 with recovery to gr ≤2 by day 15. Gr 3 non-hematologic toxicities at 4 mg/m 2 included gr 3 ALT (n=1), gr 3 AST (n=2), gr 3 hyperbilirubinemia (n=1), gr 3 hypophosphatemia (n=1), and gr 3 alkaline phosphatase elevation (n=1). Median PK values in cycle 1 at 4 mg/m 2 were: C max 473 ng/ml, AUC 0-∞ 5207 ng.hr/ml, and t½ 36 hr. AUC 0- ∞ and C max were proportional to dose. No consistent correlation was observed between DLTs and PK parameters. Stable disease for ≥ 4 cycles (range 4–11) was observed in 6 pts (4 pts at 4 mg/m 2 ; 1 pt at 6 mg/m 2 ; 1 pt at 8 mg/m 2 ). A pt with cholangiocarcinoma had evidence of radiographic tumor regression (post cycle 10) and a &gt;50% decrease in her CA 19–9. Conclusions: The recommended phase II dose of SB-743921 on the Q 21 day schedule is 4 mg/m 2 . The observed toxicities at the recommended phase II dose are manageable and reversible. The onset and duration of neutropenia is predictable. [Table: see text]
Differential expression of BCL-6, CD138/syndecan-1, and Epstein-Barr virus-encoded latent membrane protein-1 identifies distinct histogenetic subsets of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas
Authors: Antonino Carbone, Gianluca Gaidano, Annunziata Gloghini, Luigi M. Larocca, Daniela Capello, Vincenzo Canzonieri, Andrea Antinori, Umberto Tirelli, Brunangelo Falini, Riccardo Dalla-Favera
Journal: Blood (1998)
Extranodal extension is an important prognostic parameter for both colonic and rectal cancer
Authors: C. Luchini, A. Nottegar, A. Pea, M. Solmi, B. Stubbs, P. Capelli, G. Sergi, E. Manzato, M. Fassan, L.D. Wood, A. Scarpa, N. Veronese
Journal: Annals of Oncology (2016)
Abstract 18274: Under Use of Statins and LDL-C Control Among People With a Framingham 10-Year Coronary Heart Disease Risk > 20%
Authors: Christopher Gamboa, Emily Levitan, Devin Mann, Huifeng Yun, Stephen Glasser, J. Michael Woolley, Robert Rosenson, Michael Farkouh, Monika Safford, Paul Muntner
Journal: Circulation (2013)

Statins reduce the incidence of coronary heart disease (CHD) in individuals with a history of CHD or risk equivalents. A 10-year CHD risk >20% is considered a CHD risk equivalent but is frequently ...
Novel mutations in tyrosine kinase domain of epidermal growth factor receptor in prostate cancer
Authors: D. Douglas, H. Zhong, J. Ro, C. Oddoux, M. Pincus, J. Satagopan, W. Gerald, H. Scher, P. Lee, I. Osman
Journal: Journal of Clinical Oncology (2006)

4611 Background: We recently reported that EGFR protein overexpression is significantly more common in African American (AA) prostate cancer patients compared to White patients (Shuch et al. 2004 JCO, 22:4673–4677). In the current study, we further explore EGFR dysregulation in prostate cancer patients of different ethnicities by examining mutations in the EGFR tyrosine kinase (TK) domain. In addition to AA and White prostate cancer patients, we included South Korean patients in light of recent reports that EGFR mutations are more common in Asian patients with non-small cell lung cancer. Methods: Normal and tumor DNA from radical prostatectomy cases (n = 89: Koreans n = 36, AA n = 27, Whites n = 26) were studied for mutations in the EGFR TK domain using genomic DNA sequencing. Results: We identified 4/89 (5%) novel missense mutations in exons 19, 20 and 21 of TK domain: 3 in Koreans (8%, 95%, CI = 2%– 22%) and 1 in White (4%, 95% CI = 0.1%–20%) but none in AA. These mutations, which were not described before, are expected to affect TK activity based on the change of the amino acid phosphorylation pattern and the 3-dimensional structure of TK domain. We also identified 5 distinct synonymous DNA sequence changes in exons 20 and 21 in 31/89 (35%) patients. These synonymous sequence changes were not observed in the corresponding normal DNA in 8/31 (25.8%) patients, indicating the presence of de novo somatic mutation in those patients, and are likely to affect mRNA splicing leading to altered EGFR protein transcripts. Conclusions: Several independent mechanisms of EGFR dysregulation operate in prostate cancer including EGFR protein overexpression, missense mutations, and somatic synonymous sequence changes in the TK domain. Validation on a larger sample size in addition to functional studies are needed to determine the specific association between a patient’s ethnicity, EGFR dysregulation, and response to EGFR inhibitors in prostate cancer. No significant financial relationships to disclose.
Vinorelbine (NVB)-based triplet with ifosfamide (IFO) and cisplatin (NIP) as induction chemotherapy (CT) to increase resection rate in marginally unresectable non-small cell lung cancer (NSCLC) patients (pts)
Authors: M. Gottfried, R. Ramlau, M. Krzakowski, L. Novakova, A. Szczesna, J. Barcelo, R. Perng, D. Grunenwald
Journal: Journal of Clinical Oncology (2004)

7165 Background: Combined strategy CT+surgery is currently considered the best option treatment for pts with locally advanced (LA) NSCLC. A multinational phase III trial was conducted to assess additional CT on survival in completely resected tumors. Methods: After 3 cycles of NIP for LA NSCLC stage II B (only T3 N0) III A and III B (only T4 N0) and no longer than 45 days after surgery, pts were randomised to 2 additional cycles of NIP (NVB 25 mg/m2 d1, 5; IFO 3 g/m2; MESNA 3g/m2 and CDDP 80mg/m2 each at d1 qw3) (Arm A) vs to no further treatment (Arm B). Primary end-point was 2 year survival; secondaries were toxicity profile, DFS and overall survival. Results: From 1/1999 to 10/2002, 155 out of 156 pts included received CT: 133 (85%) males, median age: 59 years (35–75). Histology: 53% squamous, 30% adenocarcinoma, 5% large cell carcinoma, and 12% unknown. 65% pts were st III A, 27% II B and 8% III B. The median tumor diameter was 5.5 cm (1.2–10.6). After 3 cycles, response rate to neo-adjuvant CT was 56.5% (80/142 evaluable pts); (CI 95% [48.2–64.5]) with 3.5% CR and 53% PR. Relative dose intensity(%): 97, 99 and 99 respectively for NVB, IFO and Cisplatin. Tolerance included G3–4 neutropenia/pts in 4% and G3 anemia in 4%; non-haematological toxicities included G3 nausea/vomiting (N/V) in 11%, G3–4 diarrhoea in 3%, G3 anorexia and G3–4 infection in 6.5%, G3 asthenia 8.5% and G3–4 alopecia 25.5%. 107 pts (69%) were operated with complete resection (R0) of 74%(79/107pts). Operative mortality rate was 2.8%. After 2 to 44 days (median 21) 79 pts were randomised: 49% (37pts) in arm A (adjuvant CT) and 53% (42pts) in arm B (no adjuvant CT). Main toxicity of adjuvant CT included G3–4 N/V 6%, G3 alopecia 9% and G3 infection, G3 cardiac and G3 asthenia 1.5% each. Survival data will be submitted for May 3rd, 2004. Conclusion: The preliminary analysis of this large trial shows that the triplet NIP as neoadjuvant CT in pts with large LA NSCLC is effective, allowing 74% of R0. The administration on day 1 and 5 of NVB did reduce significantly the neutropenia, then causing no delay for surgery. No significant financial relationships to disclose.
Phase I and pharmacokinetic (PK) study of PTK787/ZK222584 (PTK/ZK) plus capecitabine (cape) in patients (Pts) with advanced cancer
Authors: R. L. Schilsky, D. Geary, L. Skoog, A. Desai, J. Valickas, E. Masson, D. Laurent, C. Pendowski, E. Vokes, M. Ratain
Journal: Journal of Clinical Oncology (2007)

3595 Background: PTK/ZK is a small molecule inhibitor of the vascular endothelial growth factor receptor family. Cape is a standard treatment for pts with breast and colon cancer, tumors for which angiogenesis inhibition is beneficial. Therefore, we conducted a phase I study of the combination to determine the maximally tolerated doses (MTD), toxicities and PK interactions. Methods: Eligible pts had advanced cancer with no standard treatment option, Karnofsky performance status (KPS) &gt; 70, and normal organ function. Pts with bone marrow or CNS involvement or who had more than 4 prior chemotherapy regimens were excluded. A dose escalation (dosesc) phase was conducted to determine the MTD followed by a dose expansion (dosexp) phase to assess PK interactions. PTK/ZK was given as a single oral daily doser without interruption and cape was given orally twice daily for 14 of 21 days. Results to Date: 43 pts (30 male, 13 female), median age 61 y (34–78 y) and median KPS 95 (70–100) were enrolled in the dosesc phase. 37 had prior chemotherapy; 5 had radiation only. Diagnoses included colorectal cancer (10), head/neck (7), sarcoma (5), renal (4), stomach/pancreas (3 each) and others (11). 29/43 pts were evaluable for MTD determination and received a total of 145 cycles. Doses of PTK/ZK-cape (mg-mg/m 2 ) were: 750/2,500; 1,000/2,500; 750/2,000; 1,000/2,000; 1,250/2,000. DLT occurred in 1/6 pts (gr 3 fatigue) at 750/2,500; 2/2 pts (≥gr 3 fatigue, hypertension [HTN]) at 1,000/2,500; 0/3 pts at 750/2,000; 2/12 pts (≥ gr 3 dizziness, HTN and seizure) at 1,000/2,000 and in 1/6 (gr 3 proteinuria) pts at 1,250/2,000. 1,250 mg was the highest PTK/ZK dose planned. Other common toxicities in the dosesc phase were hand-foot syndrome (HFS, 93%) and HTN (28%). In the dosexp phase 26 pts (14 M, 12 F) have thus far received 73 cycles at the MTD (1,250/2,000). Median age is 65 y (26–79 y) and median KPS is 80 (70–100). 28/73 cycles were delayed or interrupted for toxicity with gr ≥3 toxicities (# cycles): HFS (7), fatigue (5), increased LFTs (5), HTN (3), DVT/PE (4). 23 pts (17 in dosesc and 6 in dosexp) had response or stable disease longer than 12 weeks. Final results and PK data will be presented. Conclusion: PTK/ZK and cape can be combined without unexpected toxicities. No significant financial relationships to disclose.
Pathogenesis of Rat Colon Carcinomas Induced by &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;-nitrosourea&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Robert Lev
 4, Anthony Herp
Journal: JNCI Journal of the National Cancer Institute (1978)

Colon specimens were obtained from 45 young male and female inbred CD®F rats between 11 and 42 weeks after they began to receive intrarectal injections of the carcinogen N-methyl-N-nitrosourea (MNU) (43–108 mg, total dose); specimens were also obtained from 26 control rats. Well-developed tumors from rats receiving MNU generally presented grossly as polyps; histologically, as invasive adenocarcinomas that had not metastasized. These tumors resembled their human counterparts. Focal epithelial atypias were found in grossly normal mucosa both from rats that had not yet developed tumors and from tumor-bearing rats. Such foci typically consisted of low columnar cells with enlarged nuclei, increased number of mitoses, cytoplasmic basophilia, and reduced cytoplasmic mucus. Serial section studies of minute foci of atypia indicated that some of them arose from normal deep crypt cells. Transitions were frequently found between atypical foci and in situ or invasive carcinomas. Less commonly, adenomatous epithelium was identified in the early lesions or within the frank adenocarcinomas. It was concluded that most invasive carcinomas in this rat model originate in foci of epithelial atypia, which are found with increasing frequency in the flat mucosa during treatment with MNU, but that some carcinomas also arise from adenomatous epithelium.