313 research outputs found
Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E
Purpose This brief report describes a planned, interim, 6-patient toxicity analysis that confirms the safety of pemetrexed, carboplatin, radiation with subsequent surgery, as prescribed in the North Central Cancer Treatment Group trial N044E, in patients with locally advanced esophageal cancer. Methods Six patients with locally advanced, potentially resectable esophageal cancer received pemetrexed 500 mg/m 2 and carboplatin AUC = 6 on days 1 and 22 with 5040 centigray of concomitant radiation in 28 fractions over 5.5 weeks followed by esophagectomy as a prelude to a phase II multi-institutional trial. Results Only 1 of the 6 patients experienced a grade 4 adverse event (neutropenia). This patient also experienced a grade 3 depression. Of the remaining 5 patients, three experienced at least one grade 3 adverse event (neutropenia, nausea/vomiting, and esophagitis). There were no deaths. Incidentally, one patient manifested a complete pathologic response, three a partial pathologic response, and one stable disease. Conclusion These preliminary observations on safety suggest that this regimen can be further studied in this clinical setting
Visualizing individual microtubules using bright-field microscopy
Microtubules are filament-shaped, polymeric proteins (~25 nm in diameter)
involved in cellular structure and organization. We demonstrate the imaging of
individual microtubules using a conventional bright-field microscope, without
any additional phase or polarization optics. Light scattered by microtubules is
discriminated through extensive use of digital image-processing, thus removing
background, reducing noise and enhancing contrast. The setup builds on a
commercial microscope, with the inclusion of a minimal and inexpensive set of
components, suitable for implementation in the student laboratory. We show how
this technique can be applied to a demonstrative biophysical assay, by tracking
the motions of microtubules driven by the motor protein kinesin
Results of a planned interim toxicity analysis with trimodality therapy, including carboplatin AUC = 4, paclitaxel, 5-fluorouracil, amifostine, and radiation for locally advanced esophageal cancer: preliminary analyses and treatment recommendations from the North Central Cancer Treatment Group
PURPOSE: An aggressive trimodality approach from the Minnie Pearl Cancer Research Network [carboplatin AUC = 6, days 1 and 22; 5-fluorouracil 225 mg/m2 continuous infusion, days 1–42, paclitaxel 200 mg/m2, days 1 and 22; 45 Gy] has resulted in remarkable pathologic response rates but notable toxicity. This trial was designed to mitigate this toxicity by starting with a lower carboplatin dose, AUC = 4, and by adding subcutaneous amifostine. METHODS: This phase II trial included patients with locally advanced, potentially resectable esophageal cancer. All were to receive the above regimen with modifications of carboplatin AUC = 4 and amifostine 500 mg subcutaneously before radiation. All were then to undergo an esophagectomy. A planned interim toxicity analysis after the first 10 patients was to determine whether the carboplatin dose should escalate to AUC = 6. RESULTS: Ten patients were enrolled, and all required dose reductions/omissions during neoadjuvant therapy. One patient died from paclitaxel anaphylaxis. Six patients manifested a complete pathologic response. CONCLUSION: With this regimen, carboplatin AUC = 4 for patients with locally advanced esophageal cancer is appropriate
Composition and dynamics of the nucleolinus, a link between the nucleolus and cell division apparatus in surf clam (Spisula) oocytes
Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 287 (2012): 6702-6713, doi:10.1074/jbc.M111.288506.The nucleolinus is a little-known
cellular structure, discovered over 150
years ago (1) and thought by some
investigators in the late 19th to mid-20th
century to function in the formation of the
centrosomes or spindle. A role for the
nucleolinus in formation of the cell division
apparatus has recently been confirmed in
oocytes of the surf clam, Spisula solidissima
(2). However, we know so little about the
composition and dynamics of this
compartment, it is difficult to construct
mechanistic hypotheses or even to be sure
that prior reports were describing
analogous structures in the cells of mammals, amphibians, plants, and other
organisms where it was observed. Surf
clam oocytes are an attractive model to
approach this problem because the
nucleolinus is easily visible by light
microscopy, making it accessible by laser
microsurgery as well as isolation by
common cell fractionation techniques. In
this report we analyze the macromolecular
composition of isolated Spisula nucleolini
and examine the relationship of this
structure to the nucleolus and cell division
apparatus. Analysis of nucleolinar RNA
and protein revealed a set of molecules that
overlaps with, but is nevertheless distinct
from the nucleolus. The proteins identified
were primarily ones involved in nucleic acid
metabolism and cell cycle regulation.
Monoclonal antibodies generated against
isolated nucleolini revealed centrosomal
forerunners in the oocyte cytoplasm.
Finally, induction of damage to the
nucleolinus by laser microsurgery altered
the trafficking of α- and γ-tubulin after
fertilization. These observations strongly
support a role for the nucleolinus in cell
division and represent our first clues
regarding mechanism.This work was supported by a grant from the NIH (GM088503) to M.C.A
Long-Term Survivors of Metastatic Colorectal Cancer Treated with Systemic Chemotherapy Alone: A North Central Cancer Treatment Group Review of 3811 Patients, N0144
Although systemic chemotherapy in patients with unresectable metastatic colorectal cancer (mCRC) is palliative in nature, some patients experience long-term remission beyond 5 years consequent to treatment with chemotherapy alone
Sex and adverse events of adjuvant chemotherapy in colon cancer: an analysis of 34,640 patients in the ACCENT database
BACKGROUND: Adjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing. METHODS: The objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin). RESULTS: Data from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk. CONCLUSIONS: Our analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation
Treatment of Colorectal Peritoneal Carcinomatosis With Systemic Chemotherapy: A Pooled Analysis of North Central Cancer Treatment Group Phase III Trials N9741 and N9841
Symptoms and complications of metastatic colorectal cancer (mCRC) differ by metastatic sites. There is a paucity of prospective survival data for patients with peritoneal carcinomatosis colorectal cancer (pcCRC). We characterized outcomes of patients with pcCRC enrolled onto two prospective randomized trials of chemotherapy and contrasted that with other manifestations of mCRC (non-pcCRC)
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