LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 36

Search options

  1. Article ; Online: Impact of antecolic vs transmesocolic reconstruction on delayed gastric emptying following pancreaticoduodenectomy.

    Geng, Amber L / Thota, Bhavana / Yellanki, Sreekanth / Chen, Hui / Maguire, Ryan / Lavu, Harish / Bowne, Wilbur / Yeo, Charles J / Nevler, Avinoam

    Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract

    2024  

    Abstract: ... B or C) than TMC reconstruction, with approximately a 2-fold increase in severe DGE (OR, 1.94; 95 ...

    Abstract Background: Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy. There remains an active debate over the effect of gastrointestinal (GI) reconstruction techniques, such as antecolic (AC) or transmesocolic (TMC) reconstruction, on DGE rates. This study compared the rates of DGE between AC reconstruction and TMC reconstruction after pylorus-preserving pancreaticoduodenectomy (PPPD) and classic pancreaticoduodenectomy (PD).
    Methods: This was a retrospective analysis of a prospectively maintained pancreatic surgery database in a single, high-volume center. Demographic, perioperative, and surgical outcome data were recorded from patients who underwent a PD or PPPD between 2013 and 2021. DGE grades were classified using the International Study Group of Pancreatic Surgeons (ISGPS) criteria. Postoperatively, all patients were managed using an accelerated Whipple recovery protocol.
    Results: A total of 824 patients were assessed, with 303 patients undergoing AC reconstruction and 521 patients undergoing TMC reconstruction. The risk of DGE was significantly greater in patients who received an AC reconstruction than in patients who received a TMC reconstruction (odds ratio [OR], 1.51; 95% CI, 1.07-2.15; P < .05). In addition, AC reconstruction was shown to have a greater incidence of severe DGE (ISGPS grades B or C) than TMC reconstruction, with approximately a 2-fold increase in severe DGE (OR, 1.94; 95% CI, 1.10-3.45; P < .05). Logistic regression and propensity score matching have found increased DGE incidence with AC reconstruction (OR: 1.69 and 1.73, respectively; P < .05).
    Conclusions: Although the correlation between GI reconstruction methods and DGE remains a subject of ongoing debate, our study indicated that TMC reconstruction may be superior to AC reconstruction in minimizing the development and severity of DGE for patients after PD.
    Language English
    Publishing date 2024-03-12
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2012365-6
    ISSN 1873-4626 ; 1934-3213 ; 1091-255X
    ISSN (online) 1873-4626 ; 1934-3213
    ISSN 1091-255X
    DOI 10.1016/j.gassur.2024.03.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5207: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 354: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: A rare metastatic mesenteric malignant PEComa with TSC2 mutation treated with palliative surgical resection and nab-sirolimus: a case report.

    Meredith, Luke / Chao, Timothy / Nevler, Avinoam / Basu Mallick, Atrayee / Singla, Rajan K / McCue, Peter A / Bowne, Wilbur B / Jiang, Wei

    Diagnostic pathology

    2023  Volume 18, Issue 1, Page(s) 45

    Abstract: Background: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated ...

    Abstract Background: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of and predicting response to mTOR inhibitors in cases of malignant PEComas.
    Case presentation: Here, we report a case of an aggressive, 23 cm mesenteric malignant PEComa with multiple peritoneal metastases in a young male patient. Pathological examination of the initial biopsy showed a malignant epithelioid neoplasm with high-grade morphology and atypical immunoprofile, which precluded a definitive diagnosis. Because of the patient's excessive transfusion requirements due to intra-tumoral hemorrhage, a palliative R2 resection was performed. Histopathological examination of the tumor revealed focal immunoreactivity for Melan-A, HMB-45, desmin, and CD117. Although a diagnosis of malignant PEComa was favored, other entities such as epithelioid gastrointestinal stromal tumor (GIST) or melanoma could not be definitively ruled out. Given the favored diagnosis, the patient was started on sirolimus, an mTOR inhibitor, rather than chemotherapy. Molecular analyses were performed and the tumor was found to harbor mutations in TP53 and TSC2, supporting a definitive diagnosis of malignant PEComa. The patient was then switched to nab-sirolimus, with initial stabilization of the disease.
    Conclusions: This report details a multidisciplinary approach for the diagnosis and management of a highly aggressive, metastatic malignant PEComa in a young male patient. The basis for the treatment of malignant PEComas with the recently FDA-approved mTOR inhibitor, nab-sirolimus, is also reviewed. In summary, this case highlights the importance of molecular analysis, particularly TSC1/2 alterations, for both the definitive diagnosis of malignant PEComas and predicting their response to nab-sirolimus.
    MeSH term(s) Humans ; Male ; MTOR Inhibitors ; Mutation ; Perivascular Epithelioid Cell Neoplasms/drug therapy ; Perivascular Epithelioid Cell Neoplasms/metabolism ; Perivascular Epithelioid Cell Neoplasms/pathology ; Sarcoma ; Sirolimus/therapeutic use ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances MTOR Inhibitors ; Sirolimus (W36ZG6FT64) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; TSC2 protein, human
    Language English
    Publishing date 2023-04-11
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2210518-9
    ISSN 1746-1596 ; 1746-1596
    ISSN (online) 1746-1596
    ISSN 1746-1596
    DOI 10.1186/s13000-023-01323-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Repurposing the FDA-approved anthelmintic pyrvinium pamoate for pancreatic cancer treatment: study protocol for a phase I clinical trial in early-stage pancreatic ductal adenocarcinoma.

    Ponzini, Francesca M / Schultz, Christopher W / Leiby, Benjamin E / Cannaday, Shawnna / Yeo, T / Posey, James / Bowne, Wilbur B / Yeo, Charles / Brody, Jonathan R / Lavu, Harish / Nevler, Avinoam

    BMJ open

    2023  Volume 13, Issue 10, Page(s) e073839

    Abstract: Background: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, ... ...

    Abstract Background: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates.
    Methods and analysis: In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will be continued to a reach a maximum of 20 mg/kg orally for 3 days, if the previous two dosages (5 mg/kg and 10 mg/kg) were tolerated. Dose-limiting toxicity grade≥3 is used as the primary endpoint. The pharmacokinetic and pharmacodynamic (PK/PD) profile of PP and bioavailability in humans will be used as the secondary objective. Each participant will be monitored weekly for a total of 30 days from the final dose of PP for any side effects. The purpose of this clinical trial is to examine whether PP is safe and tolerable in patients with pancreatic cancer, as well as assess the drug's PK/PD profile in plasma and fatty tissue. Potential implications include the utilisation of PP in a synergistic manner with chemotherapeutics for the treatment of pancreatic cancer.
    Ethics and dissemination: This study was approved by the Thomas Jefferson Institutional Review Board. The protocol number for this study is 20F.041 (Version 3.1 as of 27 October 2021). The data collected and analysed from this study will be used to present at local and national conferences, as well as, written into peer-reviewed manuscript publications.
    Trial registration number: ClinicalTrials.gov: NCT05055323.
    MeSH term(s) Humans ; Drug Repositioning ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/surgery ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/surgery ; Adenocarcinoma/surgery ; Anthelmintics/therapeutic use ; Clinical Trials, Phase I as Topic ; Pancreatic Neoplasms
    Chemical Substances pyrvinium (6B9991FLU3) ; Anthelmintics
    Language English
    Publishing date 2023-10-17
    Publishing country England
    Document type Clinical Trial Protocol ; Journal Article
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2023-073839
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: KRAS mutation allele frequency threshold alters prognosis in right-sided resected pancreatic cancer.

    Nauheim, David / Moskal, David / Renslo, Bryan / Chadwick, Matthew / Jiang, Wei / Yeo, Charles J / Nevler, Avinoam / Bowne, Wilbur / Lavu, Harish

    Journal of surgical oncology

    2022  Volume 126, Issue 2, Page(s) 314–321

    Abstract: Background: Next-generation sequencing (NGS) provides information on genetic mutations and mutant allele frequency in tumor specimens. We investigated the prognostic significance of KRAS mutant allele frequency in patients with right-sided pancreatic ... ...

    Abstract Background: Next-generation sequencing (NGS) provides information on genetic mutations and mutant allele frequency in tumor specimens. We investigated the prognostic significance of KRAS mutant allele frequency in patients with right-sided pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection.
    Methods: A retrospective study reviewed patients who underwent surgical resection for PDAC and analyzed tumors with an in-house mutational panel. Microdissected samples were studied using an NGS-based assay to detect over 200 hotspot mutations in 42 genes (Pan42) commonly involved in PDAC.
    Results: A total of 144 PDAC right-sided surgical patients with a Pan42 panel were evaluated between 2015 and 2020; 121 patients (84%) harbored a KRAS mutation. Detected mutant allele frequencies were categorized as less than 20% (low mKRAS, n = 92) or greater than or equal to 20% (high mKRAS, n = 29). High mKRAS (KRAS ≥ 20%) patients were noted to have shorter disease-free survival after surgery (11.5 ± 2.1 vs. 19.5 ± 3.5 months, p = 0.03), more advanced tumor stage (p = 0.02), larger tumors (3.6 vs. 2.7 cm, p = 0.001), greater tumor cellularity (26% vs. 18%, p = 0.001), and higher rate of distant recurrence (p = 0.03) than low mKRAS patients.
    Conclusion: This study demonstrates the importance of KRAS mutant allele frequency on pathological characteristics and prognosis in right-sided PDAC treated with surgery.
    MeSH term(s) Alleles ; Biomarkers, Tumor/genetics ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/surgery ; Gene Frequency ; Humans ; Mutation ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/surgery ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics ; Retrospective Studies ; Pancreatic Neoplasms
    Chemical Substances Biomarkers, Tumor ; KRAS protein, human ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2022-03-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 82063-5
    ISSN 1096-9098 ; 0022-4790
    ISSN (online) 1096-9098
    ISSN 0022-4790
    DOI 10.1002/jso.26860
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 706: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Implementation of an opioid reduction toolkit in pancreatectomy patients significantly increases patient awareness of safe practice and decreases amount prescribed and consumed.

    Lamm, Ryan / Cannaday, Shawnna / Ponzini, Francesca / Moskal, David / Lundgren, Megan / Williamson, John E / Wummer, Brandon / Huang, Rachel / Sun, George / Song, Steven G / Im, Brian / Kowal, Luke L / Wu, Inga / Bowne, Wilbur B / Nevler, Avinoam / Cowan, Scott W / Yeo, Theresa / Yeo, Charles J / Lavu, Harish

    HPB : the official journal of the International Hepato Pancreato Biliary Association

    2023  Volume 25, Issue 7, Page(s) 807–812

    Abstract: Background: Postoperative opioid abuse following surgery is a major concern. This study sought to create an opioid reduction toolkit to reduce the number of narcotics prescribed and consumed while increasing awareness of safe disposal in pancreatectomy ... ...

    Abstract Background: Postoperative opioid abuse following surgery is a major concern. This study sought to create an opioid reduction toolkit to reduce the number of narcotics prescribed and consumed while increasing awareness of safe disposal in pancreatectomy patients.
    Methods: Prescription, consumption, and refill request data for postoperative opioids were collected from patients receiving an open pancreatectomy before and after the implementation of an opioid reduction toolkit. Outcomes included safe disposal practice awareness for unused medication.
    Results: 159 patients were included in the study: 24 in the pre-intervention and 135 in the post-intervention group. No significant demographic or clinical differences existed between groups. Median morphine milliequivalents (MMEs) prescribed were significantly reduced from 225 (225-310) to 75 (75-113) in the post-intervention group (p < 0.0001). Median MMEs consumed were significantly reduced from 109 (111-207) to 15 (0-75), p < 0.0001), as well. Refill request rates remained equivalent during the study (Pre: 17% v Post: 13%, p = 0.9) while patient awareness of safe disposal increased (Pre: 25% v Post: 62%, p < 0.0001).
    Discussion: An opioid reduction toolkit significantly reduced the number of postoperative opioids prescribed and consumed after open pancreatectomy, while refill request rates remained the same and patients' awareness of safe disposal increased.
    MeSH term(s) Humans ; Analgesics, Opioid/adverse effects ; Pancreatectomy/adverse effects ; Pain, Postoperative/diagnosis ; Pain, Postoperative/etiology ; Pain, Postoperative/prevention & control ; Opioid-Related Disorders/diagnosis ; Opioid-Related Disorders/etiology ; Opioid-Related Disorders/prevention & control ; Narcotics/therapeutic use ; Practice Patterns, Physicians'
    Chemical Substances Analgesics, Opioid ; Narcotics
    Language English
    Publishing date 2023-03-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2131251-5
    ISSN 1477-2574 ; 1365-182X
    ISSN (online) 1477-2574
    ISSN 1365-182X
    DOI 10.1016/j.hpb.2023.03.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6326: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

    Chao, Timothy / Wang, Zi-Xuan / Bowne, Wilbur B / Yudkoff, Clifford J / Torjani, Ava / Swaminathan, Vishal / Kavanagh, Taylor R / Roadarmel, Austin / Sholevar, Cyrus J / Cannaday, Shawnna / Krampitz, Geoffrey / Zhan, Tingting / Gorgov, Eliyahu / Nevler, Avinoam / Lavu, Harish / Yeo, Charles J / Peiper, Stephen C / Jiang, Wei

    Archives of pathology & laboratory medicine

    2024  

    Abstract: Context.—: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood.: Objective.—: To characterize the ...

    Abstract Context.—: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood.
    Objective.—: To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles.
    Design.—: Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed.
    Results.—: In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively).
    Conclusions.—: PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.
    Language English
    Publishing date 2024-03-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 194119-7
    ISSN 1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
    ISSN (online) 1543-2165
    ISSN 0363-0153 ; 0096-8528 ; 0003-9985
    DOI 10.5858/arpa.2023-0005-OA
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.36: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Euglycemic diabetic ketoacidosis (EDKA) after pancreaticoduodenectomy: An under-recognized metabolic abnormality with outcome implications.

    Sholevar, Cyrus / Torjani, Ava / Kavanagh, Taylor R / Yudkoff, Clifford / Xiao, Kevin / Swaminathan, Vishal / Rshaidat, Hamza / Bowne, Wilbur B / Krampitz, Geoffrey W / Nevler, Avinoam / Yeo, Charles J / Lavu, Harish

    Surgery

    2022  Volume 173, Issue 4, Page(s) 888–893

    Abstract: Background: Euglycemic diabetic ketoacidosis is a metabolic condition characterized by relative euglycemia, ketonemia, and metabolic acidosis that occurs through mechanisms resembling starvation. Pancreaticoduodenectomy is a complex abdominal operation ... ...

    Abstract Background: Euglycemic diabetic ketoacidosis is a metabolic condition characterized by relative euglycemia, ketonemia, and metabolic acidosis that occurs through mechanisms resembling starvation. Pancreaticoduodenectomy is a complex abdominal operation that subjects patients to a prolonged fasting and an inflammatory state. This study examined the incidence of euglycemic diabetic ketoacidosis and potential opportunities for early diagnosis and management in patients undergoing pancreaticoduodenectomy.
    Methods: A single-institution retrospective review of 350 patients who underwent pancreaticoduodenectomy between 2017 and 2020 was performed. Primary endpoints were peak beta-hydroxybutyrate levels, peak lactate levels, lowest pH, peak base deficits, and urinary output within the first 24 hours, postoperatively. Additional endpoints included incidence of postoperative pancreatic fistula, delayed gastric emptying, total complications, postoperative hospital length of stay, readmission rates, and changes in insulin regimen at discharge.
    Results: Of the 350 cases reviewed, 39 (11.1%) patients developed euglycemic diabetic ketoacidosis. Male sex and pancreatic cancer were associated with a risk for euglycemic diabetic ketoacidosis (P < .05). Patients with euglycemic diabetic ketoacidosis had significantly higher peak beta-hydroxybutyrate levels than patients without euglycemic diabetic ketoacidosis (mean difference = 19.8 mg/dL, 95% confidence interval = 14.7-24.9, P < .001), and were nearly four times more likely to require insulin at discharge (odds ratio 3.8, 95% confidence interval = 1.1-13.0, P < .05).
    Conclusion: This is the first large descriptive study that investigates euglycemic diabetic ketoacidosis after pancreaticoduodenectomy. Euglycemic diabetic ketoacidosis after pancreaticoduodenectomy is associated with significantly higher beta-hydroxybutyrate levels and new or increased insulin requirement at discharge. Our study demonstrates potential markers for euglycemic diabetic ketoacidosis after pancreaticoduodenectomy, offering an opportunity to identify and successfully treat this disease in a timely manner.
    MeSH term(s) Humans ; Male ; Diabetic Ketoacidosis/diagnosis ; Diabetic Ketoacidosis/etiology ; Pancreaticoduodenectomy/adverse effects ; 3-Hydroxybutyric Acid ; Acidosis/etiology ; Insulin ; Diabetes Mellitus/etiology
    Chemical Substances 3-Hydroxybutyric Acid (TZP1275679) ; Insulin
    Language English
    Publishing date 2022-08-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 202467-6
    ISSN 1532-7361 ; 0039-6060
    ISSN (online) 1532-7361
    ISSN 0039-6060
    DOI 10.1016/j.surg.2022.07.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uk I Zs.129: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: Repurposing the FDA-approved anthelmintic pyrvinium pamoate for pancreatic cancer treatment

    Benjamin E Leiby / Charles Yeo / James Posey / Avinoam Nevler / Harish Lavu / T Yeo / Francesca M Ponzini / Christopher W Schultz / Shawnna Cannaday / Wilbur B Bowne / Jonathan R Brody

    BMJ Open, Vol 13, Iss

    study protocol for a phase I clinical trial in early-stage pancreatic ductal adenocarcinoma

    2023  Volume 10

    Abstract: Background Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we ... ...

    Abstract Background Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates.Methods and analysis In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will be continued to a reach a maximum of 20 mg/kg orally for 3 days, if the previous two dosages (5 mg/kg and 10 mg/kg) were tolerated. Dose-limiting toxicity grade≥3 is used as the primary endpoint. The pharmacokinetic and pharmacodynamic (PK/PD) profile of PP and bioavailability in humans will be used as the secondary objective. Each participant will be monitored weekly for a total of 30 days from the final dose of PP for any side effects. The purpose of this clinical trial is to examine whether PP is safe and tolerable in patients with pancreatic cancer, as well as assess the drug’s PK/PD profile in plasma and fatty tissue. Potential implications include the utilisation of PP in a synergistic manner with chemotherapeutics for the treatment of pancreatic cancer.Ethics and dissemination This study was approved by the Thomas Jefferson Institutional Review Board. The protocol number for this study is 20F.041 (Version 3.1 as of 27 October 2021). The data collected and analysed from this study will be used to present at local and national conferences, as well as, written into peer-reviewed manuscript publications.Trial registration number ClinicalTrials.gov: NCT05055323.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  9. Article ; Online: Malate-aspartate shuttle promotes l-lactate oxidation in mitochondria.

    Altinok, Oya / Poggio, Juan L / Stein, David E / Bowne, Wilbur B / Shieh, Adrian C / Snyder, Nathaniel W / Orynbayeva, Zulfiya

    Journal of cellular physiology

    2019  Volume 235, Issue 3, Page(s) 2569–2581

    Abstract: Metabolism in cancer cells is rewired to generate sufficient energy equivalents and anabolic precursors to support high proliferative activity. Within the context of these competing drives aerobic glycolysis is inefficient for the cancer cellular energy ... ...

    Abstract Metabolism in cancer cells is rewired to generate sufficient energy equivalents and anabolic precursors to support high proliferative activity. Within the context of these competing drives aerobic glycolysis is inefficient for the cancer cellular energy economy. Therefore, many cancer types, including colon cancer, reprogram mitochondria-dependent processes to fulfill their elevated energy demands. Elevated glycolysis underlying the Warburg effect is an established signature of cancer metabolism. However, there are a growing number of studies that show that mitochondria remain highly oxidative under glycolytic conditions. We hypothesized that activities of glycolysis and oxidative phosphorylation are coordinated to maintain redox compartmentalization. We investigated the role of mitochondria-associated malate-aspartate and lactate shuttles in colon cancer cells as potential regulators that couple aerobic glycolysis and oxidative phosphorylation. We demonstrated that the malate-aspartate shuttle exerts control over NAD
    MeSH term(s) Aspartic Acid/metabolism ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; HCT116 Cells ; Homeostasis/genetics ; Humans ; Lactic Acid/metabolism ; Malates/metabolism ; Mitochondria/metabolism ; Mitochondria/pathology ; NAD/metabolism ; Oxidation-Reduction ; Oxidative Phosphorylation ; Warburg Effect, Oncologic
    Chemical Substances Malates ; NAD (0U46U6E8UK) ; Aspartic Acid (30KYC7MIAI) ; Lactic Acid (33X04XA5AT) ; malic acid (817L1N4CKP)
    Language English
    Publishing date 2019-09-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3116-1
    ISSN 1097-4652 ; 0021-9541
    ISSN (online) 1097-4652
    ISSN 0021-9541
    DOI 10.1002/jcp.29160
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.212: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Intraperitoneal immunotherapy: historical perspectives and modern therapy.

    Morano, W F / Aggarwal, A / Love, P / Richard, S D / Esquivel, J / Bowne, W B

    Cancer gene therapy

    2016  Volume 23, Issue 11, Page(s) 373–381

    Abstract: Intraperitoneal immunotherapy represents a novel strategy for the management of peritoneal metastases (PM). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has remained the gold standard of treatment for patients with PM, ...

    Abstract Intraperitoneal immunotherapy represents a novel strategy for the management of peritoneal metastases (PM). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has remained the gold standard of treatment for patients with PM, yet despite optimal treatment, recurrence rates remain high and long-term survival poor. From Coley's toxins to immune checkpoint inhibitors, the wide variety of anticancer immunotherapeutic strategies are now garnering attention for control of regional disease of the peritoneal cavity. Early studies with vaccine-based therapies, adoptive cell transfer, immune checkpoint inhibitors, and chimeric T cells with tumor-specific antigen receptors (CAR-T cells) are being performed, showing promise for control of peritoneal spread and induction of lasting anticancer immunity. In addition, catumaxomab, a trifunctional antibody, has been approved for intraperitoneal immunotherapy in Europe for the control of malignant ascites in patients with epithelial cell adhesion molecule positive cancers. We review a brief history of immunotherapy and current modalities under investigation for intraperitoneal use in the treatment of PM.
    Language English
    Publishing date 2016-11
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 1212513-1
    ISSN 1476-5500 ; 0929-1903
    ISSN (online) 1476-5500
    ISSN 0929-1903
    DOI 10.1038/cgt.2016.49
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4125: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top