tbuckley/cabot-search huggingface dataset:
Is more aggressive lymph node assessment associated with improved survival in stage II-III colorectal cancer? Evidence from the Surveillance, Epidemiology and End Results (SEER) cancer registry
Authors: Y. Yeh, Q. Cai, J. Chao, M. Russell
Journal: Journal of Clinical Oncology (2007)

4048 Background: NCCN guidelines recommend assessment of =12 lymph nodes (LN) to improve accuracy in colorectal cancer (CRC) staging. Previous studies have used various cut-points to assess the relationship between the number of LN sampled and survival. The association between NCCN guideline-compliant nodal sampling and survival is assessed, while controlling for other risk factors. Methods: We selected 145,485 adult patients newly diagnosed with stage II or III from SEER during 1990–2003. Kaplan-Meier curves were compared using the log-rank test. Cox proportional hazards models were constructed to determine the effect of sampling ≥ 12 LN on survival. Results: Median patient follow-up was 5.7 years. The table shows overall survival rates in CRC patients with &lt; 12 versus =12 LN assessed: After adjusting for age, sex, tumor size and grade, sampling ≥ 12 LN was independently associated with improved survival. For patients with =12 versus &lt;12 LN assessed, survival increased by 13% for stage IIa [HR=0.75; 95%CI 0.72–0.78; p&lt; .001], 16% for stage IIb [HR=0.69; 95%CI 0.67- 0.71; p&lt; .001], 12% for stage IIIb [HR=0.75; 95%CI 0.72–0.77], and 10% for stage IIIc [HR=0.85, 95%CI 0.81–0.89]. The association was not statistically significant for stage IIIa patients. Conclusion: Consistent with previous reports, this analysis found that optimal nodal sampling increased survival across stage II and III, specifically when ≥ 12 LN are sampled and when controlling for other risk factors. Furthermore, the results underscore the need for adhering to the NCCN guidelines. The lack of a statistically significant association in stage IIIa patients may be due to small cohort size. [Table: see text] [Table: see text]
Evaluation of AMG 531 in chemotherapy-induced thrombocytopenia (CIT): Results of a phase I/II study
Authors: S. Vadhan-Raj, J. Trent, D. M. Araujo, S. Patel, X. Zhou, R. S. Benjamin
Journal: Journal of Clinical Oncology (2009)

e20616 Background: AMG 531 is a Fc-peptide fusion protein (peptibody) that increases platelet production by stimulating thrombopoietin (TPO) receptors. Prior studies have shown the importance of schedule of recombinant TPO to overcome cumulative thrombocytopenia (TCP) caused by high-dose chemotherapy with carboplatin (C), a late-nadir regimen, and doxorubicin and/or ifosfamide (AI), early-nadir regimen. Methods: The objectives of this study were to evaluate the safety and biologic activity of AMG 531 in CIT. Pts receiving high dose C (AUC=11) or AI received CT alone in the study cycle-1 and CT + AMG 531 in the study cycle-2 and subsequent cycles. At least 6 pts were enrolled at each dose level of AMG 531 (1, 3, and 10 mcg/kg). AMG 531 was administered SC as 2 doses given 2 days apart, starting from the day after CT (post-dosing schedule). An additional cohort of 6 pts received AMG 531 (10 mcg/kg) 2 doses administered as predose (day -5) and postdose given on day after CT (pre-/postdosing schedule). Results: Twenty-four of the 27 pts enrolled received the study drug and are evaluable. Treatment with AMG 531 was well tolerated; one pt experienced pulmonary embolism during cycle-6. In the 4 pts that received C with AMG 531 (1 mcg/kg) by post-dosing schedule, there was a reduction in duration of TCP (days &lt; 100,000/mm3; 10 vs 7, p = 0.023, and days &lt; 50,000mm3; 6 vs 2, p = 0.001, in cycles 1 and 2, respectively) and the PLT nadir count was stable (2 pts), increased &lt; 2-fold (1 pt) or &gt; 2-fold (1 pt) in C-2 as compared to C-1. In pts that received AI with AMG 531, there was a trend for increase in PLT nadir count with pre/post dosing schedule with a regimen known to cause cumulative thrombocytopenia from C-1 to C-2 ( Table ). Conclusions: AMG 531 is well tolerated and shows biologic activity in pts receiving CT. These findings suggest that postdosing may be effective with late-nadir regimen such as C. Ongoing study will determine if pre-/postdosing may be more effective with early-nadir regimens such as AI. [Table: see text] [Table: see text]
Exocrine Pancreatic Neoplasms Induced by Methylazoxymethanol Acetate in the Guppy &lt;italic&gt;Poecilia reticulata&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J W Fournie, W E Hawkins, R M Overstreet, W W Walker
Journal: JNCI Journal of the National Cancer Institute (1987)

Exocrine pancreatic neoplasms developed in the guppy Poecilia reticulata following a single brief exposure to methylazoxymethanol acetate [(MAM-Ac) CAS: 592-62-1]. Fish 6-10 days old were exposed to concentrations of MAM-Ac up to 100 mg/liter for 2 hours. Exposed specimens were transferred to carcinogen-free water and sampled periodically for tumor development. Pancreatic neoplasms occurred in approximately 9% of histologically examined individuals exposed to 10 mg MAM-Ac/liter or less. Neoplastic lesions were not found in 122 control specimens. The neoplasms included 6 cases diagnosed as adenoma, 7 cases diagnosed as acinar cell carcinoma, and 2 cases diagnosed as adenocarcinoma. Adenomas consisted mainly of well-differentiated acinar cells that were filled with zymogen granules. Two adenomas also contained foci of atypical, less-differentiated acinar cells possessing basophilic, fibrillar cytoplasm. Acinar cell carcinomas occurred in several cellular patterns that ranged from well-differentiated to more anaplastic lesions; however, none exhibited areas of ductular proliferation. Adenocarcinomas, on the other hand, exhibited a glandular growth pattern and contained numerous ductlike structures. Both types of carcinomas appear to arise from primary acinar cells. Thus lesions probably progress from adenomas to acinar cell carcinomas and adenocarcinomas. The findings of carcinogen-induced pancreatic neoplasms in guppies further strengthen the usefulness of small fish species in carcinogen testing and provide an additional model for pancreatic tumors.
Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer
Authors: Susanne Blauwhoff-Buskermolen, Kathelijn S. Versteeg, Marian A.E. de van der Schueren, Nicole R. den Braver, Johannes Berkhof, Jacqueline A.E. Langius, Henk M.W. Verheul
Journal: Journal of Clinical Oncology (2016)

Purpose Low muscle mass is present in approximately 40% of patients with metastatic colorectal cancer (mCRC) and may be associated with poor outcome. We studied change in skeletal muscle during palliative chemotherapy in patients with mCRC and its association with treatment modifications and overall survival. Patients and Methods In 67 patients with mCRC (mean age ± standard deviation, 66.4 ± 10.6 years; 63% male), muscle area (square centimeters) was assessed using computed tomography scans of the third lumbar vertebra before and during palliative chemotherapy. Treatment modifications resulting from toxicity were evaluated, including delay, dose reduction, or termination of chemotherapy. Multiple regression analyses were performed for the association between change in muscle area and treatment modification and secondly overall survival. Results Muscle area of patients with mCRC decreased significantly during 3 months of chemotherapy by 6.1% (95% CI, −8.4 to −3.8; P &lt; .001). Change in muscle area was not associated with treatment modifications. However, patients with muscle loss during treatment of 9% or more (lowest tertile) had significantly lower survival rates than patients with muscle loss of less than 9% (at 6 months, 33% v 69% of patients alive; at 1 year, 17% v 49% of patients alive; log-rank P = .001). Muscle loss of 9% or more remained independently associated with survival when adjusted for sex, age, baseline lactate dehydrogenase concentration, comorbidity, mono-organ or multiorgan metastases, treatment line, and tumor progression at first evaluation by computed tomography scan (hazard ratio, 4.47; 95% CI, 2.21 to 9.05; P &lt; .001). Conclusion Muscle area decreased significantly during chemotherapy and was independently associated with survival in patients with mCRC. Further clinical evaluation is required to determine whether nutritional interventions and exercise training may preserve muscle area and thereby improve outcome.
Confidentiality contraception and young people. Explicit guidance at last.
Authors: Scally G
Journal: BMJ (1993)

Low teenage pregnancy rates are linked to effective sex education and provision of contraceptive services. UK contraceptive services do not adequately serve youth who are or plan on being sexually active. Most youth do not want to be involved in family planning so family planning creates an image of that which they do not want to be part. Frankness in discussing sex and provision of adequate contraceptive services in the Netherlands hints at why its adolescent pregnancy rate is only 14.3% that of England and Wales. UK youth tend not to use contraceptive services if they are not reassured about confidentiality. Confidentiality is the single most important factor in contraceptive services for UK youth. It is not clear whether some physicians would breach confidentiality in the case of patients less than 16 years old. Youth find it difficult to differentiate between physicians they can and cannot trust. A breach of confidentiality may devastate some youth. The likelihood of a youth whose physician did not maintain confidentiality reporting that physician is minimal. The General Medical Council does not have a clear statement of what is acceptable professional practice in the case of a less than 16 year old patient seeking contraception. The British Medical Association General Medical Services Committee Brook Advisory Centres Family Planning Association and the Royal College of General Practitioners have issued a joint guidance statement to be distributed to all general practitioners in November. It delineates frankly that not respecting confidentiality in cases of less than 16 year old patients seeking contraception is a serious breach of professional ethics. A strategy is needed to communicate to youth that they can trust physicians who work in general practice family planning clinics or Brook Advisory Centres. Picketing of clinics serving youth has surfaced in the UK which intimidates youth. This is unacceptable and should be stopped.
Neoepitopes and CD3-Positive and CD8-Positive Cells in Polymerase e–Mutated and Microsatellite-Instable Endometrial Cancers
Authors: Inge C. van Gool, Tjalling Bosse, David N. Church
Journal: JAMA Oncology (2016)

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Oxaliplatin (L-OHP) combined with irinotecan (CPT-11), leucovorin (LV) and fluorouracil (5-FU) compared with irinotecan, leucovorin and fluorouracil as first-line treatment for metastatic colorectal cancer (MCC): Preliminary results of a multicenter randomized phase III trial
Authors: J. Souglakos, N. Ziras, A. Polyzos, A. Athanasiadis, S. Kakolyris, T. Giannakakis, E. Tselepatiotis, K. Kalbakis, N. Vardakis, V. Georgoulias
Journal: Journal of Clinical Oncology (2004)

3532 Background: In a phase II trial conducted from our group the 4-drug regimen (5FU+LV+CPT-11+L-OHP) was highly active and well tolerated (JCO 2002;20:2661–2667). A randomized trial was conducted to compare in terms of overall survival (OS) the 4-drug regimen (Arm-A) with the “standard” 3-drug (5FU+LV+CPT-11) FOLFIRI regimen (Arm-B) as first-line treatment in MCC Methods: Assuming OS 17months for Arm-B and 21 months for Arm-A, 276 pts were needed to show a significant difference (two-tailed log-rank test; a=0.05, b=0.8). For Arm-A CPT-11 150mg/m2 30–90 min infusion was given on d1, L-OHP 65mg/m2 2h infusion on d2, simultaneously but in different lines with LV 200mg/m2 on days 2+3 followed by 5-FU 400 mg/m2/d iv bolus and 600 mg/m2/d 22h infusion on days 2+3. For Arm-B CPT-11 180mg/m2 30–90 min infusion was given on d1, LV 200 mg/m2 on days 1+2 followed by 5-FU 400 mg/m2/d iv bolus and 600 mg/m2/d 22h infusion on days 1+2. Cycles were repeated every 2 weeks until disease progression, unacceptable toxicity or consent withdrawal. Results: As of today 203 pts and 1673 cy of therapy were evaluable for safety and efficacy. 101 pts on Arm-A: M/F: 62/39, PS 0/1/2: 59/30/12, median age 65 (25–75).102 pts on Arm-B: M/F: 57/45, PS 0/1/2: 47/39/16, median age 66 (42–80). In an intention-to-treat analysis the response rate was 45% (95%CI 35,45%–55,27%) in Arm-A and 31% (95%CI 22,68%–41,24%) in Arm-B (p=0,055). In addition 32% of pts presented stable disease in Arm-A and 23% in Arm-B (p=0,147). Disease progression was observed in 23% of pts in Arm-A and 45% in Arm-B(p=0,001). Median TTP was 8.9 and 6.1 months (p=0,0958) and OS 21.1 and 16.5 months in Arm-A and Arm-B, respectively (Log rank=0,0956). Conclusions: These preliminary results show promising efficacy with acceptable safety for the 4-drug combination. Updated data will be presented. No significant financial relationships to disclose.
Comparative Carcinogenicity of Formic Acid 2-[4-(5-Nitro-2-furyl)-2-thiazolyl]hydrazide and Related Chemicals in the Rat&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E. Ertürk, J. Emory Morris, S. M. Cohen, A. M. von Esch, A. J. Crovetti, J. M. Price, George T. Bryan
Journal: JNCI Journal of the National Cancer Institute (1971)

Formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]hydrazide (FNT) previously demonstrated a high degree of carcinogenic activity in Swiss mice and Holtzman female rats. In the present study, male and female Sprague-Dawley rats and female Buffalo rats were susceptible to the carcinogenic action of FNT, which induced at high incidences mammary, renal, and hepatic tumors and tumors at other sites. To determine possible structural requirements for this activity, 2-hydrazino-4-(5-nitro-2-furyl)-thiazole, formic acid 2-[4-(2-furyl)-2-thiazolyl]hydrazide, formic acid 2-(4-methyl-2-thiazolyl)hydrazide, or 1 -formyl-3-thiosemicarbazide was fed to female Sprague-Dawley rats. In 26 rats at risk, FNT induced multiple mammary tumors in 25 rats, renal tumors in 22, liver tumors in 12, and a few tumors at other sites. In 16 rats at risk, 2-hydrazino-4-(5-nitro-2-furyl)-thiazole induced multiple mammary tumors in 15 rats and renal tumors in 3. In contrast to the marked activity of these 2 compounds, formic acid 2-[4-(2-furyl)-2-thiazolyl]hydrazide, lacking the nitro group in the 5-position on the furan ring, induced 0 tumors in 23 rats, and 1-formyl-3-thiosemicarbazide induced 5 solitary mammary tumors in 27 rats (0.50>P>0.30) (2 of 29 control rats bore solitary mammary tumors), though growth was somewhat retarded with both compounds. Intermediate in activity, formic acid 2-(4-methyl-2-thiazolyl)hydrazide induced 8 solitary mammary tumors among 28 rats at risk (P=0.034). These data suggest the nitro group in the 5-position of the furan ring plays a major, but perhaps not exclusive, role in the carcinogenic action of FNT and 2-hydrazino-4-(5-nitro-2-furyl)thiazole.
Expression of CXCR4 predicts lymph node metastasis in early breast cancer
Authors: N. Cabioglu, M. S. Yazici, B. K. Arun, T. L. Smith, G. N. Hortobagyi, J. E. Price, A. Sahin
Journal: Journal of Clinical Oncology (2004)

9525 Background: Recent experimental studies have suggested that interactions between the chemokine receptor CXCR4 and its ligand CXCL12 in host organs may play a role in breast cancer progression. There is currently no data if CXCR4 expression is associated with metastatic potential in early breast cancer. Therefore, we studied the differential expression of CXCR4 in small size lymph node positive and lymph node negative breast cancers to evaluate whether CXCR4 predicts metastasis to axillary lymph nodes. Methods: CXCR4 expression was evaluated on paraffin-embedded tissue sections obtained from patients with T1N0 (n=98) and T1N1 (n=99) breast cancer, using immunohistochemical staining. The intensity, staining percentage, and localization pattern (nuclear, cytoplasmic) were assessed, and positivity was categorized as follows: high cytoplasmic only versus others, and predominantly nuclear versus others. The expression patterns were correlated with lymph node status, and with other prognostic markers including ER/PR, bcl-2, HER2/neu and EGFR. Chi-square or Fisher's exact tests were used in categorical analyses. Results: High cytoplasmic only staining pattern was associated with increased lymph node metastasis (4% in T1N0 versus 13% in T1N1; p=0.04). In contrast, predominantly nuclear staining pattern was more frequently observed in lymph node negative patients (55% in T1N0 versus 36% in T1N1, p=0.008). Increased bcl-2 expression, previously reported as a good prognostic marker, was also more common in tumors that expressed predominantly nuclear CXCR4 compared to tumors with other staining patterns (74% vs 61%, respectively, p= 0.04). No significant correlation was identified between staining patterns of CXCR4, and ER/PR, HER2/neu or EGFR expression. Conclusion: The different staining pattern of CXCR4 (nuclear versus cytoplasmic) appears to have different biological significance for metastatic potential of breast cancer. CXCR4 expression may be a useful marker to predict lymph node metastasis in early breast cancer. No significant financial relationships to disclose.
Syndecan‐4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes
Authors: Subhamoy Das, Anthony J. Monteforte, Gunjan Singh, Marjan Majid, Michael B. Sherman, Andrew K. Dunn, Aaron B. Baker
Journal: Advanced Healthcare Materials (2016)

Delivering syndecan-4 with FGF-2 improves the effectiveness of FGF-2 therapy for ischemia in the diabetic disease state. The syndecan-4 proteoliposomes significantly enhance in vitro tubule formation as well as blood perfusion and vessel density in the ischemic hind limbs of diseased ob/ob mice. Syndecan-4 therapy also induces a marked immunomodulation in the tissues, increasing the polarization of macrophages toward the M2 phenotype.
Rapid Assays for Evaluating the Drug Sensitivity of Tumor Cells2
Authors: N. Torben Bech-Hansen, Farida Sarangi, Donald J. A. Sutherland, Vic Ling
Journal: JNCI Journal of the National Cancer Institute (1977)

Assays that assess the ability of cells to incorporate labeled precursors into acid-precipitable material in the presence of adriamycin, daunorubicin, puromycin, vinblastine, melphalan, or methotrexate were investigated as an approach to the detection of resistant cells in human tumor samples. Each assay was evaluated with suitable drug-resistant Chinese hamster ovary cell lines and normal human fibroblasts to determine whether the assays reflected the drug sensitivity of these lines. Moreover, the ability to detect the presence of drug-resistance cells in a mixed population was evaluated. Validated assays were then used to measure the drug sensitivity of cell samples from pleural and peritoneal effusions of patients, mainly with carcinoma of the breast or ovary. Though the responsiveness of the majority of the samples in these assays was similar to that of a human fetal lung fibroblast line, 37 of 142 samples displayed responses consistent with the presence of a significant proportion of drug-resistant cells. Of these 37 nonresponsive samples, 12 displayed nonresponsiveness to three drugs.
Capecitabine (C) and bevacizumab (B) for nonresectable metastatic colorectal cancer (mCRC) patients: Results from phase II AIO 0105 trial.
Authors: A. Kretzschmar, D. M. Behringer, T. Wolff, J. Zimber, S. Hegewisch-Becker, E. Kettner, K. Pflüger, A. Kirsch, N. Ziegenhagen, D. Arnold
Journal: Journal of Clinical Oncology (2010)

3555 Background: C plus B might serve as a low toxic combination for patients (pts) with mCRC not requiring intensive therapy. This is the largest prospective B plus C trial. Methods: Previously untreated pts with mCRC were to receive C (1,250 mg/sqm BID d1-14 oral) and B (7.5 mg/kg i.v.) q3w. Progression-free survival (PFS) was the primary endpoint. Second- and third-line non-cross-resistant therapies were intended. Results: From 12/06 to 09/08,a total of 72 pts were included: 38 male, median age 70 (range 50-86); 35% of pts were 75years or older (75+). ECOG PS 0/I/II: 27, 39, and 6, respectively. Synchronous metastases 45 pts, primary tumor in situ 16 pts. Treatment characteristics: Median no. of cycles 8 (range 1-24). Toxicity was mild but C had to be reduced mainly because of hand-foot- syndrome (HFS) by ≥ 30 % in 28 % of pts and by ≥ 50% in 10%. For worst CTC grades in % by pts see the Table. One pt suffered a perforation that resulted in death. Efficacy:ORR was 32%: CR 5 pts and PR 18 pts. Median follow-up is 25 months (mos.) and median PFS was 6.2 (range 1-24) mos. for all (with 6.2 for 75+; 6.9 for younger), but was 9.0 mos. for ECOG 0 pts.. Median OS was 18 mos. for all pts. and 27 mos. for ECOG 0 pts. OS was only 10.5 mos for 75+. Salvage therapy: Any kind of second- and third-line systemic therapy was given to 64% and 47% of pts, respectively. However, only 25% of pts received both oxaliplatin (Ox) and irinotecan (Iri). 19% received Anti-EGF-R-MAB (EGF). 75+ pts rarely (36%) received any non-cross-resistant drug (i.e., Oxa, Iri, EGF) and only one of them (4%) got both Ox and Iri. Conclusions: PFS was shorter than reported by other trials. OS might be influenced by the inclusion of older patients who finally did not receive subsequent treatment lines although the opposite was the intention of the trial. Our data does not support B plus C as standard for for older pts or pts with impaired ECOG-PS. To further test the strategy with strict inclusion criteria a randomized comparison with non inferiority design is initiated by the AIO study group. CTC grade/event Hypertension Fatigue Hand-foot syndrome Diarrhea Nausea Vomiting Bleeding Thrombosis I° (% of pts) 7 18 17 13 18 7 13 4 II° (% of pts) 8 6 19 13 6 3 0 4 III° (% of pts) 3 1 22 6 4 1 0 8 IV° (% of pts) 0 0 0 1 0 0 0 1 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche
Human Cytomegalovirus Inhibited Megakaryocytic Differentiation, Maturation and Induced Apoptosis in Vitro.
Authors: Jian Liang Chen, Godfrey ChiFung Chan, Jie Yu Ye, Zheng Xian He, Qing Wen Wang, Si Nian Pan, Xiao Feng Li, Rui Xia Deng, Mo Yang
Journal: Blood (2009)