tbuckley/cabot-search huggingface dataset:
Nanoparticle albumin-bound (Nab) paclitaxel (P) in combination with bevacizumab (B) with and without gemcitabine (G): Early experience at the Braman Family Breast Cancer Institute
Authors: C. F. Lobo, G. Lopes, O. Silva, S. Gluck
Journal: Journal of Clinical Oncology (2006)

10748 Background: Nab-P improves outcomes when compared against single agent cremophor-based P, as does the addition of bevacizumab or gemcitabine to the same agent. There are no available data regarding combinations of Nab-P with B and/or G. Ongoing investigational efforts are evaluating various doublets with these agents, but, to the best of our knowledge, not all 3 of them in the same regimen. All drugs are currently FDA-approved in the treatment of breast cancer. Methods: Review of single-institution experience, evaluating safety and preliminary evidence of activity with the use of Nab-P and B with and without G in heavily pretreated her2neu negative metastatic breast cancer patients. Assessment of response was undertaken by the investigators independently of treating physician. RECIST criteria were used. Three patients received Nab-P and B at the following doses: Nab-P 100 mg/m 2 , B 10 mg/kg every 2 weeks, and 2 patients received all 3 drugs as follows: Nab-P 100 mg/m 2 , G 1,000 mg/m 2 , B 10 mg/kg every 2 weeks. Results: Five women have been evaluated. Median age was 51 (range 34–69). Two patients had hormone-receptor positive disease and 3 had ER/PR/Her2neu-negative cancer. Prior number of regimens was 3 (range 2–7). Four patients had been treated with a taxane. One received both paclitaxel and docetaxel, and 3 docetaxel only. A median of 5 cycles have been administered (range 3–9). First-cycle grade 3/4 toxicity was seen in only one patient who had a baseline grade 2 thrombocytopenia that progressed to grade 3. The thrombocytopenia resolved without requiring transfusion and without any hemorrhagic complication. Another patient developed grade 2 peripheral neuropathy. Two patients are not yet assessable for response. At time of first evaluation 1 patient had progressive disease (Nab-P, B; 7 prior lines of treatment), one had stable disease (Nab-P, B, G; 3 prior lines of therapy, including docetaxel), and 1 had a partial response (Nab-P, B, G; 2 prior therapies, including docetaxel). Conclusions: These very preliminary data suggest that Nab-P in combination with B with and without G is a safe regimen and formal Phase I/II trials are being developed to confirm its clinical activity. [Table: see text]
Putting on the style
Authors: M. Cooter
Journal: BMJ (1999)

Imagine that your paper has been accepted by the BMJ . After the work of writing and revision, you are looking forward to seeing it in print and receiving the acclaim of colleagues. The proofs arrive. You settle down to read your hard-wrought prose—and revel in how well it reads. Then you notice the “? to author” inserted here and there. To answer some of these queries, you turn back to your original— and realise how much has been changed. You wonder what's been done to your paper. Was this really necessary?

Like every paper published in the BMJ , yours will have undergone scrutiny by a technical editor. These invisible professionals are the most exacting readers of the paper. Their scrutiny and revision adds value by making your paper clear, concise, and accurate. Their mission is to remove …
A phase I pharmacokinetic and pharmacogenomic study of E7070 administered once every 21 days
Authors: Y. Yamada, N. Yamamoto, T. Shimoyama, A. Horiike, Y. Fujisaka, K. Takayama, T. Sakamoto, Y. Nishioka, S. Yasuda, T. Tamura
Journal: Journal of Clinical Oncology (2004)

2030 Background: E7070 is a sulphonamide derivative being developed as an anticancer agent. In vitro studies indicate that the drug disrupts the G1/S phase of the cell cycle, thereby inducing cell cycle arrest and apoptosis. The objectives of this phase I study of E7070 in Japanese patients were to estimate the maximal tolerated dose (MTD), determine the recommended dose for phase II, establish the pharmacokinetic profile of E7070 and examine its relation to polymorphisms of CYP2C9 (*2, *3) and CYP2C19 (*2, *3), and seek preliminary evidence of efficacy. Methods: Patients received 1–2 hr iv infusions of E7070 (400, 600, 700, 800 or 900 mg/m2) on Day 1 of a 21-day cycle. Dose-limiting toxicity (DLT) was defined as G4 leukopenia, G4 neutropenia lasting 5 days or with fever ≥ 38.5°C, thrombocytopenia (less than 25,000/μL), and G3 non-hematologic toxicity (except nausea/vomiting or alopecia). Results: Twenty-one patients (age 35–70 years, M/F 15/6, 15 colorectal, 2 SCLC, 4 others) received between 1 and 8 cycles of E7070. DLT was observed in 0/3, 0/3, 0/6, 1/6 and 2/3 patients assigned to each dose level. MTD was 900 mg/m2. DLT comprised leukopenia, neutropenia, thrombocytopenia, elevation of aspartate aminotransferase, colitis, and ileus. The mean area under the curve (AUC) for successive dose levels increased in a non-dose-proportional manner (1066, 4204, 3300, 3498 and 6106 μg*hr/mL, respectively). Two patients (10%) were mutant heterozygous for CYP2C9. As for CYP2C19, eight patients (38%) were wild type and the remainder were mutant heterozygous or homozygous. The AUCs of patients with mutant alleles were higher than those of patients with wild type for all dose levels. The severity of toxic effects such as myelosuppression seemed to depend on AUC. No partial responses were observed. One patient completed 8 cycles of treatment at a dose of 700 mg/m2, with a maximum tumor volume reduction of 19%. Conclusions: A dose of 800 mg/m2 was recommended for further phase II studies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Co., Ltd.
Combined Pan-HER and ALK/ROS1/MET Inhibition with Dacomitinib and Crizotinib in Advanced Non–Small Cell Lung Cancer: Results of a Phase I Study
Authors: Pasi A. Jänne, Alice T. Shaw, D. Ross Camidge, Giuseppe Giaccone, S. Martin Shreeve, Yiyun Tang, Zelanna Goldberg, Jean-François Martini, Huiping Xu, Leonard P. James, Benjamin J. Solomon
Journal: Journal of Thoracic Oncology (2016)
Diagnostic efficacy of current imaging tools to detect pulmonary embolism in lung cancer: Correlation with tumor size, histology and anatomical location
Authors: C. Rathnasabapathy, S. G. Naik, H. Chenthilmurugan, S. Kodali, S. Sivamurthy, M. Kalavar
Journal: Journal of Clinical Oncology (2008)

20717 Background: Computerized tomography (CT) is widely used in the diagnosis and staging of lung cancer. To assess the diagnostic efficacy of current imaging tools to detect pulmonary embolism (PE) in lung cancer in correlation with tumor size, location and histopathology. Methods: We reviewed data of 98 patients with confirmed histopathologic diagnosis of lung cancer between January 2005 and December 2007. All patients had CT chest with contrast.CT angiography performed for patients, with suspected PE. Results: Demographics of 98 patients (M: 52, F: 46) had: African American: 71, others:14, Hispanic: 12. CT chest categorized tumor sizes as follows: <2cm: 1(1.04%), 2–5 cm: 58 (59.18%), 5–10cm: 31 (32.3%), >10cm: 8 (8.33%).Out of these 98 patients 45 patients had stage IV disease and 33 patients had stage III disease. Right upper lobe lesions (n=38) were the most common primary tumor findings on the CT scan of the chest followed by lesions in left upper lobe (n=27), right lower lobe (n=11) and left lower lobe (n=7), right middle lobe (n=4), hilar (n=8), mediastinal (n=2) and sub carinal (n=1) lesion. Pulmonary embolism was seen on contrast CT chest in none of the 98(0.00%) patients. CT angiography revealed pulmonary embolism in 5 (83.33%) out of the 6 CT angiograms done among these patients. The incidence of pulmonary embolism in patients with lung cancer did not correlate with histology, tumor size. Interestingly 3 out of 5 (60%) patients with pulmonary embolism on CT angiogram had right upper lobe lesions. All the patients with pulmonary embolism had stage IV disease. Conclusions: CT angiography with PE protocol seems to be a better modality for detecting pulmonary emboli compared to conventional CT chest with contrast in patients with lung cancer. Stage of the disease (stage IV) but not tumor size and histology seems to be associated with occurence of pulmonary embolism. No significant financial relationships to disclose.
P-175 Oncolytic Virus Therapy in Pancreatic Cancer: Clinical Efficacy and Pharmacodynamic Analysis of REOLYSIN in Combination with Gemcitabine in Patients with Advanced Pancreatic Adenocarcinoma
Authors: D. Mahalingam, S. Goel, M. Coffey, N. Noronha, G. Selvaggi, S. Nawrocki, G. Nuovo, M. Mita
Journal: Annals of Oncology (2015)
Incidence of human papillomavirus in head and neck squamous cell carcinomas
Authors: M. V. Jaglal, P. Desai, G. Schaefer, D. M. Miller, S. Ghim, P. Gopal, F. Hanan, A. B. Jenson
Journal: Journal of Clinical Oncology (2008)

17020 Background: Papillomaviruses (PVs) cause neoplasias of squamous cells, resulting in benign, premalignant and malignant lesions. The highly carcinogenic HPVs (16 and 18) cause cancer by infection of metaplastic epithelial squamous cells. E6 and E7 are over expressed in HPV-induced cancers and are required for maintaining the malignant state. In the majority of head and neck squamous cell carcinomas caused by HPV, pathway disruption occurs via inactivation of the p16 gene thereby causing p16 overexpression. Methods: Surgical pathology records were searched for cases diagnosed as neck lymph nodes with metastatic squamous cell carcinoma from January 1, 2000 to July 31, 2007, which yielded 41 patients. Formalin fixed paraffin embedded blocks from neck masses were examined using PCR sequencing using MY 09/11 and GP 5/6 primers sets as well as staining for the p16INK biomarker. Demographics were studied to determine trends of confounding factors. Results: 41 patients were evaluated with the mean age of 56 ± 10. 34 were male and 7 were female. The overall HPV incident rate was 12/41 (29%) by PCR and an additional 10% of samples were positive by p16 staining. Overall, 11 samples were positive by both PCR and p16 staining, 1 was positive with only PCR, and 4 additional samples were positive with p16 staining only. HPV subtypes were determined by sequencing the positive PCR product yielding 10/12 HPV 16, 1/12 HPV 33, and 1/12 HPV 45. All patients in the study were documented smokers. 39/41 patients had at least occasional documented alcohol usage - the two that denied alcohol use were both HPV positive. Conclusions: In this study, 29% of the samples were positive for HPV using PCR. An additional 10% of samples were positive by P16 staining, which is more sensitive, but not as specific for HPV. Since HPV has been documented to be positive prognostic indicator in men, HPV staining is recommended on all squamous head and neck carcinomas. Future direction of studies may include whether the HPV is simply present in these samples causing a predisposition to HNSCC or whether the HPV is integrated into the DNA and producing E6 and E7 causing deactivation of tumor suppressing genes. Regardless, given this high incidence rate of HPV, vaccination of both genders should be considered. No significant financial relationships to disclose.
Phase II Trial Of Medium-Dose VP-16, Cyclophosphamide and Total-Body Irradiation Conditioning Regimen Before Allogeneic Stem Cell Transplantation For Acute Lymphoblastic Leukemia In Adults
Authors: Tatsunori Goto, Akio Shigematsu, Makoto Onizuka, Shin Fujisawa, Ritsuro Suzuki, Yoshiko Atsuta, Kazuo Hatanaka, Masayoshi Masuko, Toshiro Ito, Naoki Kobayashi, Jun Kato, Koichi Miyamura, Takahiro Fukuda, Yasuo Morishima, Masahiro Imamura
Journal: Blood (2013)
A phase II study of neoadjuvant FOLFOX4 and cetuximab (C) in patients with locally advanced rectal adenocarcinoma (RA).
Authors: B. H. Chao, N. K. LoConte, W. R. Schelman, D. Mulkerin, M. S. Huie, J. C. Eickhoff, K. D. Holen
Journal: Journal of Clinical Oncology (2010)

e14122 Background: For resectable RA, 5-fluorouracil (5FU) with radiotherapy (RT) has been used commonly in the neoadjuvant setting. In metastatic colorectal cancer (CRC), C and FOLFOX4 as first-line treatment has shown promising results (Bokemeyer et al, JCO 2009). This phase II study was to investigate the down-staging rate (DSR) of C and FOLFOX4 as neoadjuvant chemotherapy (CT) for resectable, locally advanced RA. Methods: Eligible patients had resectable RA, T3/4 or any T with N1/2 staged by transrectal ultrasound (TRUS), no prior pelvic RT, and no prior anticancer therapy for CRC. Patients received FOLFOX4 and C 400 mg/m2 D1 followed by 250 mg/m2 weekly in a 28-day cycle for 2 cycles. TRUS was done before and after 2 cycles. In patients achieving partial response (PR) by RECIST criteria, 2 further cycles were given before total mesorectal excision, followed by 2 additional cycles of CT. RT with infusional 5FU was given neoadjuvantly in patients who did not achieve PR or adjuvantly in those with pathologic T3/4 or node positive disease at surgery. The primary endpoint was DSR. Seven confirmed responses in 11 patients were required to complete enrollment of 25 patients, with 19 (75%) needed to declare efficacy (Simon-Optimal design). Results: Six patients (2 male, 4/2 ECOG PS 0/1, 6 T3, 1/5 N0/1) were enrolled between 4/08 and 11/09. The study was closed to accrual because of withdrawal of funding. Toxicity data are available for 6 patients (Table). Four patients had grade 3/4 toxicities. Four patients achieved PR, one stable disease, and one progressive disease. All patients with PR had tumor down staging at surgery (DSR 67%), none of whom required adjuvant RT. One patient had a complete pathologic response. Conclusions: Neoadjuvant C and FOLFOX4 is a tolerable regimen that appears effective in down-staging locally advanced RA. In the setting of no RT, this is promising and warrants further evaluation in a larger clinical trial. Adverse events Any grade, n (%) Grade 3/4, n (%) Neutropenia 6 (100) 3 (50) Neuropathy 4 (67) 1 (17) Fatigue 4 (67) 1 (17) Rash 4 (67) 0 Hypokalemia 3 (50) 2 (33) AST 2 (33) 1 (17) ALT 2 (33) 1 (17) Mucositis 2 (33) 0 Nausea 2 (33) 0 Diarrhea 2 (33) 0 Abbreviations: AST, aspartate aminotransferase; ALT, alanine transaminase. No significant financial relationships to disclose.
Health of adolescents is targeted in new UN strategy
Authors: Anne Gulland
Journal: BMJ (2015)

Global health initiatives are focusing on the health of adolescents for the first time, with the launch of a new United Nations strategy to improve the health of women, children, and adolescents.1

In a foreword to the strategy, launched alongside the formal adoption of the UN sustainable development goals2—the successors to the millennium development goals—the UN secretary general, Ban Ki-moon, said that adolescents were “central to everything we want to achieve, and …
Cross-sex supervision for cross-sex therapy
Authors: A Alonso, J S Rutan
Journal: American Journal of Psychiatry (1978)

The female supervisor can help the male therapist in training to overcome problems in cross-sex therapy by presenting herself as a role model, providing relevant literature, and sharing her own experiences as a woman and as a professional. By enabling the male trainee to identify safely with a woman in a position of relative power, she can help him to deal with the intrinsic limitations of empathy and with other problems, such as "countertransference deafness," that may block his work with female patients.
Correlation of primary tumor engraftment in immune deficient mice and relapse rate in patients with early-stage non-small cell lung carcinoma (NSCLC)
Authors: T. John, M. Li, D. Panchal, F. Hui, F. Meng, B. Bandarchi-Chamkhaleh, D. Kohler, C. Zhu, F. A. Shepherd, M. Tsao
Journal: Journal of Clinical Oncology (2009)

11082 Background: Compared to cell lines, primary tumor xenografts potentially are more clinically relevant cancer models as they more closely reflect the phenotype and genotype of the original cancer. However, only a minority of tumors engraft successfully in severe combined immune deficient (scid) mice and can be passaged serially. Although xenograft models are used extensively, few studies have investigated whether tumors that engraft represent a distinct clinical subset. We hypothesized that NSCLC tumors with more aggressive clinical and histological features have greater engraftment capacity than those with a less aggressive phenotype. Methods: Fresh primary tumors were harvested from NSCLC patients who underwent curative resection. Tumor fragments were implanted into the subcutaneous tissue of non-obese diabetic-scid mice within 24 hrs of excision. Patient characteristics for tumors that engrafted (XG) and did not engraft (No-XG) were compared. Only tumors from patients with &gt;1-yr follow-up were evaluated for time to progression (TTP) and to correlate clinicopathological features with engraftment. Results: Between March 2005 and October 2008, 110 tumors were implanted. Of these, 45 (41%) engrafted and were passaged serially in vivo. The histological features of the primary were retained in 93% of XG tumors. Squamous cell carcinomas engrafted significantly more than adenocarcinomas (57% versus 26%, p=0.03). There were no significant differences in differentiation grade or clinical stage between the XG and No-XG groups. XG patients had significantly shorter TTP than the No-XG group (10.19 versus 18.64 months, p=0.003). In multivariate analysis the ability to form a xenograft was an independent predictor of relapse (HR 4.15 95% CI 1.152–14.94, p=0.03). Conclusions: Xenograft models can be established from the histological spectra of NSCLC encountered in the clinical setting and mimic closely the features of their primary tumors. The capacity of these tumors to engraft may be predictive of a more aggressive phenotype and poorer clinical outcome. No significant financial relationships to disclose.
Complement synthesis in the injured kidney
Authors: S H Sacks, W Zhou, N S Sheerin
Journal: Journal of the American Society of Nephrology (1996)

On pages 2428 to 2433 of this issue, Miyazaki et al. provide evidence that complement component C3 is synthesized within the glomeruli of patients with mesangial glomerulonephritis. Although it has been known for several years that cells isolated from the human kidney can synthesize a range of complement components, and that immune complex disease can increase the expression of these genes, it is only now that the link between intraglomerular synthesis of complement and human glomerulonephritis can be made. In view of the long interest in the role of complement in the pathogenesis of glomerulonephritis, this begs the question to what extent local complement synthesis may be involved in the generation of tissue injury. Given also the double-sided nature of complement-proinflammatory and protective-It remains to be seen if the roles of local and systemic complement differ in these respects. To weigh these questions, we examine the current evidence that connects local complement synthesis with renal injury, and ask what studies are needed to provide more definitive answers.
Validation of the Criteria of Response to Treatment In AL Amyloidosis.
Authors: Giovanni Palladini, Angela Dispenzieri, Morie Abraham A Gertz, Ashutosh Wechalekar, Philip N Hawkins, Stefan O Schonland, Ute Hegenbart, Raymond L. Comenzo, Efstathios Kastritis, Meletios A. Dimopoulos, Arnaud Jaccard, Catherine Klersy, Giampaolo Merlini
Journal: Blood (2010)
Depressed Mood and Subsequent Physical Illness
Authors: Evelyn L. Goldberg, George W. Comstock, Robijn K. Hornstra
Journal: American Journal of Psychiatry (1979)

The authors describe the results of a matched case-control analysis in which 82 pairs of subjects were selected from a large-scale community study carried out in two general populations. Cases were those of persons hospitalized during an interval between two interviews for an illness starting during that interval or persons who died during the interval. Controls were persons with no new illnesses or hospitalizations during the interval. No relationship between measures of depressive symptomatology or depressed mood and subsequent physical illness was shown. This result corroborates the findings of prospective studies in more selected populations and suggests that it is unlikely that depressed mood is related to subsequent physical illness.
A phase I study of the novel, third generation epothilone ZK-EPO in patients with advanced solid tumors
Authors: P. Schmid, P. Kiewe, D. Kuehnhardt, A. Korfel, S. Lindemann, M. Giurescu, S. Reif, E. Thiel, K. Possinger
Journal: Journal of Clinical Oncology (2005)

2051 Background: Epothilones are a new class of cytotoxic agents that induce tubulin polymerization. ZK-EPO, the only fully synthetic, third-generation analogue of epothilone B, is a highly potent tubulin stabilizer that has shown substantial preclinical antitumor activity, including against taxane-resistant models. This Phase I study was initiated to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of ZK-EPO in patients with advanced solid tumors. Secondary objectives were to determine the safety, tolerability, pharmacokinetics and antitumor activity of ZK-EPO. Methods: Patients with histologically confirmed advanced solid tumors that were resistant/refractory to conventional antineoplastic treatment (n=44), or for whom no standard therapy was available (n=3), were enrolled on the trial. ZK-EPO was given as a 30-minute intravenous infusion once every 3 weeks; the starting dose was 0.6 mg/m2, and dose levels were escalated using a modified Fibonacci design. Treatment was continued until disease progression or unacceptable toxicity occurred. Results: To date, 47 patients (median age 54 years; range 25–80) have received a total of 151 courses of ZK-EPO (median 3; range 1–23) at 12 dose levels up to 29 mg/m2. The most common adverse events were peripheral sensory neuropathy (mostly grade 1–2; 16 patients) and nausea (8 patients). Hematological toxicity was mild and infrequent (grade 2 leukopenia in 2 patients). Dose-limiting grade 3 (Common Toxicity Criteria) peripheral neuropathy and grade 3 ataxia occurred at 16 mg/m2 (1 patient) and 29 mg/m2 (1 patient), respectively. No other DLTs have been observed, and the MTD has not been reached. Two confirmed partial remissions were observed in patients with taxane-pretreated breast cancer (one with taxane resistant disease) receiving 12 and 16 mg/m2 ZK-EPO, respectively. Stable disease lasting up to 16+ months (median 5.5; range 3–16+) was observed in 13 patients (NSCLC, cholangiocarcinoma, head and neck cancer, uveal melanoma, and adrenal carcinoma). Conclusions: The trial is ongoing and the MTD for ZK-EPO has not been reached. Preliminary data indicate that ZK-EPO is well tolerated, with antitumor activity observed in 15 patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering AG, Berlin, Germany Schering AG, Berlin, Germany