tbuckley/cabot-search huggingface dataset:
Importance of maintenance of dose intensity (DI) during induction chemotherapy (iCT) for metastatic nonseminomatous germ cell tumors (NSGCT)
Authors: M. Fedyanin, A. Tryakin, D. Titov, T. Zakharova, I. Fainstein, K. Figurin, B. Polockii, J. Sergeev, A. Garin, S. Tjulandin
Journal: Journal of Clinical Oncology (2009)

e16063 Background: Cisplatin- and etoposide-based CT allows curing the majority of patients (pts) with metastatic germ cell tumor. There are limited data concerning the importance of maintenance of DI during iCT. In the retrospective study we analyzed the role of DI of iCT on metastatic NSGCT. Methods: 589 chemotherapy-naïve pts with advanced NSGCT received induction iCT from 1987 to 2006 in our center. We compared data of all pts who relapsed after iCT (147 pts) with data of 159 randomly sampled pts without relapses. During iCT all pts received classical E 500 P (24%) or BE 500 P (76%) regimens. Median follow-up time was 49 (range, 3–218) months. Eighty four (27.5%) of 306 pts, 107 (35%) and 115 (37.5%) were from good, intermediate and poor prognostic groups, respectively. DI was calculated for every drug and expressed in mg/m 2 per week. Multivariate Cox stepwise regression analysis was performed to determine independent prognostic factors in each IGCCCG prognostic group. Progression free survival was used as endpoint of the analysis. Results: Multivariate analysis revealed the following negative prognostic factors as independent: in pts of the IGCCCG good prognostic group: retroperitoneal lymph nodes &gt;5 cm (HR 3.53, 95% Cl 1.66–7.51). In pts with the intermediate prognosis: DI of etoposide &lt;80% (HR 4.73; 95 % CI 4.85–25.04) and presence of pulmonary metastases (HR 0.45, 95% Cl 0.203–0.977). In IGCCCG poor prognostic group: DI of etoposide &lt;80% (HR 1.82, 95% Cl 1.143–2.913). Conclusions: Maintaining a DI of greater then 80% of etoposide during iCT, for the treatment metastatic NSGCT, is one of the crucial factors for pts outcome, particularly in intermediate and poor IGCCCG prognostic groups. No significant financial relationships to disclose.
Combined transpapillary drainage and endoscopic ultrasound-guided hepaticoduodenostomy after failed manipulation under cholangioscopy guidance
Authors: Yasuki Hori, Kazuki Hayashi, Itaru Naitoh, Michihiro Yoshida, Makoto Natsume, Hidenori Sahashi, Hiromi Kataoka
Journal: Endoscopy (2020)

For unresectable malignant hilar biliary obstructions, drainage of ≥ 50 % of the liver volume is recommended [1]. Endoscopic transpapillary biliary drainage is the current standard treatment for malignant hilar biliary obstruction. Cholangioscopy-assisted guidewire placement is a useful method for biliary drainage, which can be used even in patients without contrast-filled images [2]
Pharmacodynamics and pharmacokinetics of AUY922 in a phase I study of solid tumor patients
Authors: S. Ide, M. Motwani, M. R. Jensen, J. Wang, N. Huseinovic, P. Stiegler, X. Wang, C. Quadt
Journal: Journal of Clinical Oncology (2009)

3533 Background: AUY922 is a synthetic inhibitor of Heat Shock Protein 90. Disruption of the HSP90 chaperone hetero- complex results in the loss of repression of heat shock factor-1 (HSF1), and subsequent induction of HSP70. We evaluated HSP70 as a pharmacodynamic (PD) marker of AUY922 activity in a phase I/II clinical trial in patients (pts) with solid tumors. Methods: Single agent AUY922 was administered by IV infusion once a week to pts with advanced solid malignancies. HSP70 levels in PBMC were quantitated by ELISA in samples taken at baseline and multiple time-points post the 1 st and 5 th treatments over two cycles. Fold change of HSP70 induction was calculated and compared to dose level and AUY922 blood exposure obtained within the first week of treatment (single dose) at 6, 24, 48, and 168 hours post-treatment. Results: Of the 40 pts treated to date, HSP70 levels in PBMC has been evaluated in 36, encompassing seven dose levels ranging from 2 mg/m 2 to 40mg/m 2 . Baseline levels of HSP70 in PBMC ranged from 26.0 to 95.1 ng/mg protein, with a median of 42.5ng/mg. The highest level of HSP70 induction obtained over two cycles was increasing with dose from 2 to 40 mg/m 2 , with a range of 1.4 to 12.1 fold, and the amount of HSP70 induction was frequently higher in the second cycle of treatment. In the first cycle of treatment, HSP70 induction is correlated to blood AUC. The degree of HSP70 upregulation in PBMCs at 40 mg/m 2 exceeds the 8-fold upregulation seen in BT474 xenograft tumor tissue when treated with efficacious doses of AUY922. Conclusions: PK/PD analyses show that the highest level of HSP70 achieved post-treatment increases with dose, and at the highest dose tested thus far (40mg/m 2 ), this pharmacodynamic effect has not yet reached a maximum response. Additionally, our analysis suggests that in humans, the PD effect of AUY922 is reaching the level corresponding to that required for anti-tumor effect in the BT474 xenograft model. [Table: see text]
Tumor phenotype and characteristics of metastatic brain involvement in breast cancer patients: Potential clinical consequences
Authors: M. Palacova, M. Svoboda, P. Fabian, B. Ondrova, P. Grell, G. Jana, D. Princ, L. Radova, P. Slampa, R. Vyzula
Journal: Journal of Clinical Oncology (2009)

1026 Background: Central nervous system metastases (CNS) occur in about 20% of patients with breast cancer. Despite the fact that most of these patients die within a few months, substantial subgroup may survive a year or more. Methods: We performed this study on cohort of 187 breast cancer patients who developed CNS metastases to identify relations between the tumor phenotype and the incidence and characteristics of CNS dissemination, response to the local therapy and overall survival since the development of metastases in brain (OScns). Results: The incidence of monitored phenotypes and other data are included in the table. An unambiguous dependence between the tumor's phenotype and the following attributes has been proven: a) interval between the disease diagnosis and the 1 st metastatic event (DFS); b) interval between the 1 st metastatic event and the metastases in the CNS (TTPcns); c) characteristics of CNS dissemination. The CNS dissemination was the most extensive in patients with HER-2+ tumors in comparison with HER-2 negat. carcinomas. Surprisingly, patients with triple-negative tumors had the minimal metastatic involvement of CNS defined by size and number of lesions. Phenotype did not correlate with local response to therapy and OScns. The OScns has been significantly prolonged by neurosurgery (median 13,8 vs 2,4 months, p&lt;0.0001) and when the effective local treatment was followed by system treatment (6,1 vs 1,9 months, p&lt;0.0001). Conclusions: Our study has confirmed the dependence between primary tumor phenotype and the time of incidence of metastatic brain affection and character of their spread. Our results encourage the inclusion of CNS imaging examination (CT or MRI) into the regular restaging of patients with HER2 positive and triple-negative primary breast cancer, who are at high risk for early development of CNS dissemination. Especially in case of triple-negative tumors, there is higher probability for early detection of limited CNS metastatic involvement. [Table: see text] No significant financial relationships to disclose.
AB0092 Polyarteritis nodosa presenting with bilateral perirenal hematoma in patient with fmf
Authors: M Çalgüneri, S Apras, MA Öztürk, V Çobankara, S Kiraz, I Ertenli, B Çil, A Oto
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> <h3>Methods</h3> Case Report: A 17-year old Turkish boy was admitted to our clinic with complaints of weight loss, fatigue and abdominal pain. He had been on colchicine therapy for 6 years with the diagnosis of FMF. On January 2000, he was diagnosed as having acute hepatitis A infection in another centre. Two weeks later he was hospitalised due to severe abdominal pain and abrupt decrease in his haemoglobin values. A right renal subcapsular hematoma was demonstrated by computerised tomography (CT). During follow-up haemoglobin values progressively declined and the hematoma showed enlargement in control CT. Therefore right nephrectomy was performed. After the patient was stabilised he was discharged. However he was again hospitalised with similar complaints 4 days later. This time subcapsular hematoma was demonstrated in the left kidney and he was referred to our hospital in March 2000. In physical examination, blood pressure was 160/125 mmHg. Laboratory evaluation demonstrated anaemia and elevated erythrocyte sedimentation rate and C-reactive protein. Serological tests for anti-hepatitis B surface antigen, anti-hepatitis A IgG and IgM were positive. Nephrectomy slides were re-evaluated in our pathology department. Patchy and segmental areas of renal infarct were demonstrated. No amyloid deposits could be noted in the histopathology specimens. Renal angiography demonstrated 2 microaneurisms on intertubular arteries. Together with these findings the diagnosis of PAN was made and the patients was treated with intravenous corticosteroids, intravenous cyclophosphomide and oral corticosteroids together with antihypertensive therapy. He is still being followed-up by our clinic in good health. <h3>Results</h3> <h3>Conclusion</h3> Perirenal hematoma, which is a rare complication of isolated PAN, have been reported in approximately half of the patients with FMF who developed PAN. The exact pathogenetic relationship of FMF and PAN also is not clear. Immune-related mechanisms have been demonstrated in FMF. It has been proposed previously that infection-related antigenic stimuli could trigger the development of vasculitides. In the present case an usual response to hepatitis A infection and/or previous hepatitis B infection might have been among the triggers of vasculitic process. Additional reports demonstrating direct causal relationship between infectious agents and vasculitic syndromes in patients with FMF will help us to clarify the relationship between the two disorders.
Bundling of mRNA strands inside polyion complexes improves mRNA delivery efficiency in vitro and in vivo
Authors: Kyoko Koji, Naoto Yoshinaga, Yuki Mochida, Taehun Hong, Takuya Miyazaki, Kazunori Kataoka, Kensuke Osada, Horacio Cabral, Satoshi Uchida
Journal: Biomaterials (2020)
Anti-vascular activity by TZT-1027 induces direct cytotoxicity against human breast cancer in vitro and in vivo
Authors: Rieko Nakamura, Tetsuro Kubota, Yoshiro Saikawa, Jun-Ichi Koh, Yoshinori Yamada, Yoshihide Otani, Masahiko Watanabe, Koichiro Kumai, Masaki Kitajima, Jun-Ichi Watanabe, Motohiro Kobayashi
Journal: Cancer Research (2004)

4557  BackgroundTZT-1027 is a newly synthesized derivative of dolastatin 10, from the Indian Ocean sea hare, Dolabella auricularia, as a potent antitumor agent against several murine tumors. While apoptosis and G2/M arrest are reported to be one of mechanisms for growth inhibition against tumors as direct toxicity, indirect antitumor toxicity of TZT-1027 is reported to be possible via selective shut-down of tumor blood supply. PurposeIn the study, we attempted to clarify the antitumor mechanism of TZT-1027, of which might be based on both/either direct action (apoptosis, cell cycle arrest) and/or indirect action (anti-vascular activity ), using human breast cancer cell lines. Materials and Methods: TZT-1027 was synthesized in the Pharmacological Research Department, Teikoku Hormone Mfg. Co., Ltd. Human breast cancer cell lines, MCF-7 and R-27, were used for the in vitro experiments. The in vitro antitumor activity of TZT-1027 was evaluated by MTT assay at various concentrations of TZT-1027, for 24, 48 and 72 h. The in vivo study was designed using Human breast cancer xenografts, MCF-7 and R-27, which were subcutaneously inoculated into the bilateral dorsum of female nude mouse supplemented with 5 mg estradiol per kg. In vitro collagen gel droplet-drug sensitivity test (CD-DST) was performed using both xenografts. In the study evaluating anti-vascular activity, 1 or 2 mg of TZT-1027 per kg was injected iv into nude mice bearing R-27, and Evans blue was injected to assess the time-lapse change of tumorous blood flow by TZT-1027, comparing with normal renal organ. ResultsTZT-1027 showed a concentration-dependent cytotoxicity against MCF-7 cells after 48 and 72 hours of incubation, but R-27 was resistant to TZT-1027, in vitro. A time-dependent effect was not obvious in the in vitro experiment. In in vivo study, MCF-7 and R-27 were sensitive to TZT-1027, as the lowest T/C value and RW of MCF-7 were 25.5% and 0.312, respectively, and those of R-27 were 28.6% and 0.8, respectively. In evaluating actual tumor weights, there were statistically significant differences between the control and TZT-1027 group in both xenografts. In CD-DST, MCF-7 was sensitive to TZT-1027 (IC50= 3,400 pg/ml), however R-27 was resistant to TZT-1027. In the Evans blue study using R-27, TZT-1027 blocked tumor blood flow up to half of the untreated control, from 1 h to 24h after TZT-1027-injection. The 2 mg/kg TZT-1027 group had continuously suppressed blood flow until 8 mg at 6 h and 9 mg at 24 h of Evans blue per tumor weight in g after injection. In the 1-mg/kg TZT-1027 group, the Evans blue contents in the tumor were 14 mg/g at 6 and 24 h after TZT-1027 injection. ConclusionsTZT-1027 demonstrated its antitumor activity through direct cytotoxicity for MCF-7, as well as selective anti-vascular action for R-27.
AB0080 Treatment failure pulmonary haemorrhage of sistemic lupus
Authors: S Holgado, A Olivé, M Gumà, V Ortiz-Santamaría, M Valls, A Lafont, E Casado, X Tena
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To describe the treatment and outcome of patients with SLE and pulmonary haemorrhage. <h3>Methods</h3> Retrospective study (1989–2000). Centre: Universitary Hospital. Area: 700,000 inhabitans. SLE clinic: 154 SLE patients were reviewed. All patients fulfilled the ACR criteria for SLE. <h3>Results</h3> All patients received plasmapheresis, 3 bolus of cyclophosphamide 12 mg/kg/day and prednisone 2 mg/kg/day iv. Mechanical ventilation was employed in all patients. Death was secondary to nosocomial infections. <h3>Conclusion</h3> Pulmonary haemorrhage is a rare and often fatal complication of SLE. There are no uniform recommendations for treatment. Mechanical ventilation and inmunosupresors were a risk factor for a increase mortality.
Reciprocal regulation of pancreatic ductal adenocarcinoma growth and molecular subtype by HNF4α and SIX1/4
Authors: Soledad A Camolotto, Veronika K Belova, Luke Torre-Healy, Jeffery M Vahrenkamp, Kristofer C Berrett, Hannah Conway, Jill Shea, Chris Stubben, Richard Moffitt, Jason Gertz, Eric L Snyder
Journal: Gut (2020)

Objective Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival of less than 5%. Transcriptomic analysis has identified two clinically relevant molecular subtypes of PDAC: classical and basal-like. The classical subtype is characterised by a more favourable prognosis and better response to chemotherapy than the basal-like subtype. The classical subtype also expresses higher levels of lineage specifiers that regulate endodermal differentiation, including the nuclear receptor hepatocyte nuclear factor 4 α (HNF4α). The objective of this study is to evaluate the role of HNF4α, SIX4 and SIX1 in regulating the growth and molecular subtype of PDAC. Design We manipulate the expression of HNF4α, SIX4 and SIX1 in multiple in vitro and in vivo PDAC models. We determine the consequences of manipulating these genes on PDAC growth, differentiation and molecular subtype using functional assays, gene expression analysis and cross-species comparisons with human datasets. Results We show that HNF4α restrains tumour growth and drives tumour cells toward an epithelial identity. Gene expression analysis of murine models and human tumours shows that HNF4α activates expression of genes associated with the classical subtype. HNF4α also directly represses SIX4 and SIX1, two mesodermal/neuronal lineage specifiers expressed in the basal-like subtype. Finally, SIX4 and SIX1 drive proliferation and regulate differentiation in HNF4α-negative PDAC. Conclusion Our data show that HNF4α regulates the growth and molecular subtype of PDAC by multiple mechanisms, including activation of the classical gene expression programme and repression of SIX4 and SIX1, which may represent novel dependencies of the basal-like subtype.
Bone health practices in men on androgen deprivation therapy (ADT): A population-based analysis of 25,802 patients
Authors: S. M. Alibhai, M. Duong-Hua, R. Sutradhar, A. M. Cheung, N. E. Fleshner, P. Warde, L. Paszat
Journal: Journal of Clinical Oncology (2009)

9631 Background: ADT is used in up to 1 in 2 men with prostate cancer. Osteoporosis and fragility fractures are important side effects of ADT. Guidelines recommend 2 important bone health practices for men on ADT - measurement of bone mineral density with dual x-ray absorptiometry (DEXA) and use of bisphosphonates in men at risk of osteoporosis. The implementation of these guidelines in practice is not well known. Methods: Using linked administrative databases, we identified 25,802 men (mean age 75.9 y, range 66–100 y) with prostate cancer who were treated with at least 6 months of ADT or who underwent bilateral orchiectomy in Ontario, Canada between 1995 and 2005. Performance of DEXA and prescription of bisphosphonates were captured using specific procedure codes and drug identification numbers, respectively. Prior use of DEXA and bisphosphonates, as well as prior diagnoses of osteoporosis and fragility fracture, were captured with specific diagnostic codes and a 3 y look-back period. Annual rates per 100 person-years were determined for both outcomes. Results: Among 25,802 men, 3.09% had a DEXA more than one year prior to starting ADT, and 3.14% had a prior diagnosis of osteoporosis. Within 2 years of starting ADT, the rate of undergoing DEXA rose from 0.50 per 100 person-years in 1995 to 19.47 in 2005. Rates of DEXA testing were higher among those with a prior diagnosis of osteoporosis, prior DEXA test, or prior fragility fracture but did not reach rates above 50 per 100 person-years in any of these groups. Bisphosphonate use increased from 0.27 per 100 person-years in 1995 to 3.18 in 2005 among prior non-users. More men on ADT were started on a bisphosphonate in the third year after starting ADT as compared to the second year, and rates were higher in year 2 than year 1. Less than one-third of men starting a bisphosphonate underwent any DEXA testing within 12 months of bisphosphonate initiation. Conclusions: Rates of DEXA testing and bisphosphonate use have increased over time among older men starting ADT, but significant gaps and delays remain in the quality of bone health care in this population. No significant financial relationships to disclose.
Selpercatinib Aimed at<i>RET</i>-Altered Cancers
Authors: Razelle Kurzrock
Journal: New England Journal of Medicine (2020)

A remarkable increase has occurred in the number of highly targeted drugs that have efficacy in patients with advanced cancers that harbor specific genomic alterations. Prime examples are the NTRK inhibitors that target NTRK fusions, which are found in only approximately 0.3% of cancers.1,2 As many as 75% of the patients with tumors that bear NTRK fusions and who have received these agents have had a response. These results have led to the Food and Drug Administration (FDA) approval of the use of the NTRK inhibitors larotrectinib and entrectinib in adult and pediatric patients with NTRK fusion–positive solid tumors, regardless . . .
Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis
Authors: H. Ishigami, J. Kitayama, S. Kaisaki, A. Hidemura, M. Kato, K. Otani, T. Kamei, D. Soma, H. Miyato, H. Yamashita, H. Nagawa
Journal: Journal of Clinical Oncology (2009)

4542 Background: A phase II study to evaluate the efficacy and tolerability of weekly intravenous and intraperitoneal paclitaxel combined with S-1 was performed in gastric cancer patients with peritoneal metastasis. Methods: Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. Paclitaxel was administered intravenously at 50 mg/m 2 and intraperitoneally at 20 mg/m 2 on days 1 and 8. S-1 was administered at 80 mg/m 2 /day for 14 consecutive days, followed by 7 days rest. The primary endpoint was the 1-year overall survival rate. Secondary endpoints were the response rate, efficacy against malignant ascites and safety. Results: Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination confirmed by staging laparoscopy, 13 with peritoneal recurrence, and 6 with positive peritoneal cytology only. The median number of courses administered was 7 (range 1–23). The 1-year overall survival rate was 78% (95% CI, 65–90%). The overall response rate was 56% (95% CI, 32–79%) in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The incidences of grade 3/4 hematological and non- hematological toxicities were 40% and 15%, respectively. The frequent grade 3/4 toxicities included neutropenia (38%), leukopenia (18%), anemia (10%), and nausea (8%). Catheter obstruction observed in one patient was the only complication related to the peritoneal access device or intraperitoneal infusion. There were no treatment-related deaths. Conclusions: Combination chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis. No significant financial relationships to disclose.