bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dephosphorylation of inner arm 1 is associated with ciliary reversals in Tetrahymena thermophila
Authors: Deckman Cassandra M. , Pennock David G. 
Published: December 2003

AbstractIn many organisms, depolarizing stimuli cause an increase in intraciliary Ca2+, which results in reversal of ciliary beat direction and backward swimming. The mechanism by which an increase in intraciliary Ca2+ causes ciliary reversal is not known. Here we show that Tetrahymena cells treated with okadaic acid or cantharidin to inhibit protein phosphatases do not swim backwards in response to depolarizing stimuli. We also show that both okadaic acid and cantharidin inhibit backward swimming in reactivated, extracted cell models treated with Ca2+. In contrast, treatment of whole cells or extracted cell models with protein kinase inhibitors has no effect on backward swimming. These results suggest that a component of the axonemal machinery is dephosphorylated during ciliary reversal. The phosphorylation state of inner arm dynein 1 (I1) was determined before and after cells were exposed to depolarizing conditions that induce ciliary reversal. An I1 intermediate chain is phosphorylated in forward swimming cells but is dephosphorylated in cells treated with a depolarizing stimulus. Our results suggest that dephosphorylation of Tetrahymena inner arm dynein 1 may be an essential part of the mechanism of ciliary reversal in response to increased intraciliary Ca2+. Cell Motil. Cytoskeleton 57:73–83, 2004. © 2004 Wiley‐Liss, Inc.
Overexpression of profilin reduces the migration of invasive breast cancer cells
Authors: Roy Partha , Jacobson Ken 
Published: December 2003

AbstractThe exact role profilin plays in cell migration is not clear. In this study, we have evaluated the effect of overexpression of profilin on the migration of breast cancer cells. Overexpression was carried out by stably expressing GFP‐profilin in BT474 cells. It was observed that even a moderate level of overexpression of profilin significantly impaired the ability of BT474 cells to spread on fibronectin‐coated substrate and migrate in response to EGF. GFP‐profilin expressing cells also showed increased resistance to detachment in response to trypsin and increased tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin compared to the parental and GFP‐expressing (control) cell lines. These results suggest that perturbation of profilin levels may offer a good strategy for controlling the metastatic potential of breast cancer cells. Cell Motil. Cytoskeleton 57:84–95, 2004. © 2004 Wiley‐Liss, Inc.
Maturation of DC is associated with changes in motile characteristics and adherence
Authors: Burns Siobhan , Hardy Samantha J. , Buddle Joanna , Yong Kwee L. , Jones Gareth E. , Thrasher Adrian J. 
Published: December 2003

AbstractMigration of dendritic cells (DC) from sentinel sites to lymphoid tissue entails the initiation and coordination of a complex series of cytoskeletal rearrangements resulting in polarised protrusion, formation of new adhesion points, and detachment. Although many diverse receptor‐ligand interactions stimulating DC maturation and migration have been identified, the changes that occur in the structure of the actin cytoskeleton during these processes have received little attention. When derived in vitro, immature DC floated in clumps, and upon addition of maturation stimuli such as lipopolysaccharide (LPS), they rapidly adhered, developed polarity, and assembled actin‐rich structures known as podosomes at the leading edge of the cell. Podosome assembly was associated with the specific recruitment of β2 integrins, which in the absence of the Wiskott Aldrich Syndrome protein (WASp), did not occur. As maturation progressed, normal DC once again became rounded and devoid of podosomes. This change in morphology was closely associated with a quantitatively reduced ability to adhere to fibronectin or ICAM‐1‐coated surfaces. In immature DC, failure to form podosomes or selective inhibition of the CD18 component of podosomes resulted in a similarly reduced ability to adhere to ICAM‐1, indicating that podosomes, through CD18, are necessary for tight adhesion to this ligand. We, therefore, propose that podosomes provide an essential link between directional cell protrusion and achievement of DC translocation by establishing new dynamic anchor points at the front of the cell. The temporal regulation of podosome assembly during DC maturation also suggests that they may be most critical for early movement, perhaps during transmigration of lymphatic endothelium. Cell Motil. Cytoskeleton 57:118–132, 2004. © 2004 Wiley‐Liss, Inc.
Is breast cancer survival improving?
Authors: Giordano Sharon H. , Buzdar Aman U. , Smith Terry L. , Kau Shu‐Wan , Yang Ying , Hortobagyi Gabriel N. 
Published: December 2003

AbstractBACKGROUNDDespite advances in therapies for breast cancer, improvement in survival for patients with recurrent or metastatic breast cancer has been difficult to establish. The objective of the current study was to determine whether the survival of women with recurrent breast cancer has improved from 1974 to 2000.METHODSThe authors analyzed the survival experience of 834 women who developed recurrent breast cancer between November 1974 and December 2000. All patients had been treated previously with adjuvant anthracycline‐based protocols. Patients were divided into five consecutive groups based on year of breast cancer recurrence, and survival was compared across the five groups. Because some prognostic variables were divided unevenly divided among the cohorts, a multivariate model was created to determine the association of year of recurrence and survival after accounting for other prognostic factors.RESULTSIn the unadjusted analysis, there was a statistically significant improvement in survival across the five groups, and the more recent cohorts had longer survival (P< 0.001). Other variables that predicted longer survival after breast cancer recurrence included smaller initial tumor size, lower stage of disease, fewer lymph nodes involved, longer disease‐free interval, estrogen receptor–positive tumors, and nonvisceral dominant site of disease recurrence. In the multivariate analysis, which adjusted for these prognostic factors, year of recurrence was associated with a trend toward improved survival, with a 1% reduction in risk for each increasing year.CONCLUSIONSFor these cohorts of patients, the authors present data suggesting that the prognosis for patients with recurrent breast cancer improved between 1974 and 2000. Cancer 2004;100:44–52. © 2003 American Cancer Society.
Rare ductal adenocarcinoma of the pancreas in patients younger than age 40 years
Authors: Lüttges Jutta , Stigge Claudia , Pacena Maike , Klöppel Günter 
Published: December 2003

AbstractBACKGROUNDPancreatic ductal adenocarcinomas (PDACs) are extremely rare before age 40 years. The objective of the current study was to determine whether the features of PDACs in patients age < 40 years differ from those in older patients. The authors reviewed the literature and their own files.METHODSThe cases reported in the literature were evaluated to determine their precise diagnoses and characteristic features. In a series of 439 PDACs from the authors' files, tumors in patients age < 40 years were identified, and their clinicopathologic features and certain genetic features were compared with those in a selected group of patients age > 40 years.RESULTSOf 71 pancreatic carcinomas reported in patients age < 40 years, only 20 fully qualified as PDACs. The remaining tumors represented malignancies other than PDACs, such as pancreatoblastoma, solid‐pseudopapillary neoplasms, acinar cell carcinomas, and endocrine tumors. PDACs in patients age < 20 years were the absolute exception and commonly were associated with risk factors such as Peutz–Jeghers syndrome, hereditary pancreatic cancer syndrome, and preceding radiotherapy. In the authors' series of patients, there were 6 PDACs and 4 PDAC variants in patients age < 40 years (0.2%), all in male patients. These tumors compared well with the PDACs in patients age > 40 years in their pathologic and molecular findings. Three patients were age ≤ 20 years, and 2 of those patients had a mucinous component with MUC2 positivity.CONCLUSIONSThe incidence of PDACs in patients age < 40 years was approximately 0.3%, and the incidence in patients age < 20 years was 0.1%. Their clinicopathologic findings were comparable to those in patients age > 40 years, but they seemed to include more variants, particularly mucinous carcinomas. In addition, PDACs in younger patients frequently appeared to be associated with genetic factors. Cancer 2004;100:173–82. © 2003 American Cancer Society
The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase
Authors: Sneed Thomas B. , Kantarjian Hagop M. , Talpaz Moshe , O'Brien Susan , Rios Mary Beth , Bekele B. Nebiyou , Zhou Xian , Resta Debra , Wierda William , Faderl Stefan , Giles Francis , Cortes Jorge E. 
Published: December 2003

AbstractBACKGROUNDImatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45% of patients with CML reportedly experience myelosuppression ≥ Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown.METHODSThe authors analyzed 143 patients with late chronic‐phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response.RESULTSNeutropenia ≥ Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and thrombocytopenia ≥ Grade 3 occurred in 31 patients (22%). Any myelosuppression ≥ Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58% with Grade ≥ 3 myelosuppression compared with a rate of 75% without Grade ≥3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response.CONCLUSIONSMyelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated. Cancer 2004;100:116–21. © 2003 American Cancer Society.
A Phase II trial of suramin monthly × 3 for hormone‐refractory prostate carcinoma
Authors: Vogelzang Nicholas J. , Karrison Theodore , Stadler Walter M. , Garcia Juan , Cohn Helene , Kugler John , Troeger Thomas , Giannone Leonard , Arrieta Rose , Ratain Mark J. , Vokes Everett E. 
Published: December 2003

AbstractBACKGROUNDThe goal of the current study was to determine the prostate‐specific antigen (PSA) and objective response rates and the pharmacokinetics associated with a monthly × 3 one‐hour infusion of suramin in 58 patients with hormone‐refractory prostate carcinoma.METHODSA PSA response was defined as a > 50% reduction in the PSA level from baseline for at least 3 consecutive evaluations over a minimum of 6 weeks. The suramin dose was 2400 mg/m2 taken intravenously on Day 1, 1620 mg/m2 on Day 29, and 1292 mg/m2 on Day 57. All patients received 0.5 mg dexamethasone twice daily.RESULTSAmong 56 evaluable patients (median entry PSA level, 229.5 ng/mL), there were 21 PSA responders (37.5%). Among 27 patients with measurable disease, there were 5 responders (4 partial and 1 complete). The median overall survival time was 15.3 months. Grade III fatigue (14.1%) was the predominant toxicity observed. Suramin plasma levels remained high even 3 months after treatment was discontinued. Among the 12 evaluable patients who previously had received chemotherapy, the PSA response rate was 42%; one response was observed among 4 patients with measurable disease, and the median survival was 12 months.CONCLUSIONSMonthly bolus suramin was well tolerated, reduced PSA levels, and induced objective responses, even in patients who previously had received chemotherapy. Cancer 2004;100:65–71. © 2003 American Cancer Society.
Prolonged survival after complete resection of metastases from intraocular melanoma
Authors: Hsueh Eddy C. , Essner Richard , Foshag Leland J. , Ye Xing , Wang He‐Jing , Morton Donald L. 
Published: December 2003

AbstractBACKGROUNDThe median survival time is only 2–6 months after a diagnosis of metastases from intraocular melanoma. Because complete resection of metastatic melanoma from a cutaneous primary tumor can prolong survival, the authors hypothesized that resection also might benefit patients with metastases from an intraocular site.METHODSFrom 1971 to 1999, 112 patients with metastatic melanoma from an intraocular site were enrolled in various treatment protocols after informed consent was obtained. Prospectively recorded clinical variables and follow‐up information were retrieved from the patient database. Survival curves were estimated using the Kaplan–Meier method. Univariate analysis was performed with the log‐rank test. Multivariate analysis was performed using the Cox proportional hazards regression model. Propensity score analysis was used to reduce the imbalance between subgroups and to assess treatment effect.RESULTSSeventy‐eight patients (70%) presented with liver involvement. Twenty‐four patients (21%) underwent resection of metastatic lesions. At a median follow‐up time of 11 months (range, 1–97 months; > 36 months for survivors), the median survival period was 11 months and the 5‐year survival rate was 7%. Univariate analysis showed that surgical resection, site of metastases, number of metastatic lesions, and disease‐free interval were correlated significantly with survival (P < 0.001, P < 0.001, P < 0.001, and P = 0.031, respectively). Multivariate analysis showed that surgical resection was significant (P = 0.008) but that the site of metastases was not (P = 0.146). The median survival and the 5‐year survival rate were 38 months and 39%, respectively, for surgical patients, versus 9 months and 0%, respectively, for nonsurgical patients. After adjusting for covariate imbalance by propensity score analysis, surgery remained significant (P = 0.021) on multivariate analysis.CONCLUSIONSComplete resection may prolong survival in certain patients with distant metastases from intraocular primary melanoma. However, the overall unfavorable prognosis indicates an urgent need for more effective nonsurgical interventions. Cancer 2004;100:122–9. © 2003 American Cancer Society.
Association of nonmelanoma skin cancer with second malignancy
Authors: Rosenberg Carol A. , Greenland Philip , Khandekar Janardan , Loar Aimee , Ascensao Joao , Lopez Ana Maria 
Published: December 2003

AbstractBACKGROUNDHeightened risks of second cancers have been reported in patients with nonmelanoma cancer of the skin (NMSC), but this association has not been studied in a large, ethnically diverse, multigeographic population.METHODSThis cross‐sectional study assessed the association of NMSC with another malignancy in the Women's Health Initiative Observational Study, a study that was conducted in 40 communities throughout the U.S. and involved 93,676 postmenopausal women ages 50–79 years. Cancer history, demographics, and previous and current risk exposures were determined by questionnaire at a baseline examination. Logistic regression was used to assess the association (odds ratio) of a history of NMSC with a history of other (non‐NMSC) cancers controlling for age and potential confounding factors. Complete cancer data were available in 92,658 women.RESULTSIn age‐adjusted analyses, women with a history of NMSC (n = 7554 women) were 2.30 times as likely to report a history of another cancer, other than NMSC, compared with women who had no history of NMSC (95% confidence interval [95% CI], 2.18–2.44). In a subgroup analysis, black women with NMSC had 7.46 times the odds (95% CI, 3.08–18.0) of reporting a second malignancy compared with black women without NMSC.CONCLUSIONSThis study provides additional evidence of an association between NMSC and another malignancy in a large, multiethnic population. Cancer 2004;100:130–8. © 2003 American Cancer Society.
The significance of isolation of saprophytic molds from the lower respiratory tract in patients with cancer
Authors: Lionakis Michail S. , Kontoyiannis Dimitrios P. 
Published: December 2003

AbstractBACKGROUNDInvasive infections caused by molds other thanAspergillus,Fusarium, andZygomyceteshave been reported sporadically in patients with leukemia and allogeneic bone marrow transplantation (BMT). However, the significance of lower respiratory tract cultures that are positive for these saprophytic molds in an unselected population of patients with cancer remains unclear.METHODSThe authors evaluated the significance of respiratory specimens positive for saprophytic molds in patients with cancer using the criteria set by the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG). They included the diagnostic category of indeterminate pulmonary invasive mold infection (IMI) for cases that met the criteria for probable IMI but had other pathogens concomitantly isolated from the respiratory tract.RESULTSEighty‐five cases with at least 1 positive culture were identified in 79 patients. Two cases were proven IMI, 29 were indeterminate IMI, 5 were possible IMI, and 49 were no IMI. All 38 cases from patients with solid tumors represented colonization compared with only 11 of the 47 cases (23%) from high‐risk patients (P< 0.0001). The positive predictive value (PPV) of cultures was 0% in patients with solid tumors and ranged from 4.3% to 76.6%, depending on the analytic model used, in high‐risk patients with leukemia and recipients of BMT. Cultures positive forScedosporiumspp. had a higher PPV (9.1–100%) than did cultures positive for non‐Scedosporiumspp. (2.8– 69.4%).CONCLUSIONSAdjustments of the EORTC/MSG criteria may be required for the diagnosis of invasive infections caused by saprophytic molds, especially non‐Scedosporiumspp., in patients with cancer. Cancer 2004;100:165–72. © 2003 American Cancer Society.
Correlation of tumor volume and surface area with lymph node status in patients with multifocal/multicentric breast carcinoma
Authors: Andea Aleodor A. , Bouwman David , Wallis Tracie , Visscher Daniel W. 
Published: December 2003

AbstractBACKGROUNDMulticentric breast carcinomas have a higher frequency of axillary lymph node metastasis than unifocal tumors of similar stage. It remains unclear whether this merely reflects larger tumor volumes or a different biologic behavior. The authors have shown previously that when aggregate tumor diameter are used for staging, unifocal and multifocal tumors have a similar frequency of axillary lymph node metastasis. However, summing diameter overestimates actual tumor volume because volume is proportional to the third power of the diameter. Therefore, the aim of the current study was to reanalyze the relation between size and axillary lymph node status by correcting for tumor volumes and surface areas.METHODSVolumes and surface areas of 122 breast tumor specimens with multiple macroscopic nodules (two foci: n = 95; three foci: n = 22; three foci: n = 5) were calculated by approximating the shape of each tumor nodule to an ellipsoid (for volume) or to a prolate spheroid (for area). For comparison, the authors used an internal control series, comprised of 469 macroscopic unifocal tumors. For all patients, multiple assessments of largest tumor size and combined size of all foci were correlated with the status of axillary lymph nodes. The associations between lymph node status, tumor volume or area, and multifocality were modeled using univariate and multivariate logistic regression.RESULTSWhen either the largest or the aggregate tumor volume was used as a size estimate, tumor specimens with multiple nodules had a higher frequency of lymph node involvement compared with unifocal tumors of a similar volume or area. The odds ratio (OR) for having positive lymph nodes was 2.34 for aggregate volume measurement (P < 0.001). Surface area estimates yielded similar results (OR = 2.2, P < 0.001).CONCLUSIONSBreast tumors with multiple macroscopic nodules had a different biology, with a propensity to dissemination at smaller tumor volumes (i.e., there was another factor besides volume alone that accounted for the differences in behavior). Cancer 2004;100:20–7. © 2003 American Cancer Society.
Uncertain benefit from surgery in patients with lung metastases from breast carcinoma
Authors: Planchard David , Soria Jean‐Charles , Michiels Stefan , Grunenwald Dominique , Validire Pierre , Caliandro Raffaele , Girard Philippe , Le Chevalier Thierry 
Published: December 2003

AbstractBACKGROUNDIsolated lung metastases have been reported to occur in 10–20% of all women with breast carcinoma. The authors described a series of patients who underwent surgery for lung metastases from breast carcinoma.METHODSThey reviewed the files of 125 consecutive patients who underwent surgery with a curative intent for lung metastases from breast carcinoma between 1972 an 1998 at a single institution. Survival curves were plotted by the Kaplan–Meier method. Prognostic factors were identified using the log‐rank test and a Cox proportional hazards model for univariate and multivariate analyses, respectively.RESULTSThe median age at surgery was 53 years. There was a median of 1 resected metastasis (range, 1–16 resected metastases). The median size of the largest metastasis was 19 mm (range, 5–70 mm). The median disease‐free interval (DFI) was 3 years. The median follow‐up time after surgery was 8.5 years (range, 25 days to 22 years). The 3‐year, 5‐year, and 10‐year probabilities of survival were 58% (95% confidence interval [95% CI], 49–67%), 45% (95% CI, 36–55%), and 30% (95% CI, 21–41%), respectively. The median survival time after surgery was 4.2 years. Complete resection was achieved in 96 patients. The quality of the resection (complete vs. incomplete) was not a statistically significant prognostic factor by univariate analysis and there was no significant difference between these two groups in terms of adjuvant postoperative therapy. The characteristics of the primary tumor and the number of metastases (one vs. two or more) had no detectable influence on survival. The size of the largest metastasis (> 20 mm or ≤ 20 mm) and the DFI (≤ 3 years vs. > 3 years) were highly significant prognostic factors (P = 0.006 and P = 0.003, respectively). This was confirmed by multivariate analysis. Patients with a DFI ≤ 3 years and/or the largest metastasis > 20 mm reportedly had a poor outcome (median survival, 2.6 years vs. 8.5 years for patients with none of these poor prognostic factors).CONCLUSIONSResection of lung metastases from breast carcinoma was associated with a significant 5‐year survival rate of 45%. Whether these encouraging findings resulted from the surgical procedure itself or the preoperative selection of patients remained uncertain. When surgery is considered in this setting, the size of the largest metastasis and the DFI should be taken into account. Cancer 2004;100:28–35.© 2003 American Cancer Society.