Publications by authors named "Klute K"

Local and systemic immunosuppression are prominent features of pancreatic cancer, rendering anti-tumor effector cells inactive and immunotherapeutic approaches ineffective. The spleen, an understudied point of antigen-presentation and T cell priming in humans, holds particular importance in pancreatic cancer due to its proximity to the developing tumor. As main effectors of antigen presentation, dendritic cells display antigens to lymphocytes, thereby bridging the innate and adaptive immune response.

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: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Currently, surgical resection is the only potentially curative treatment. Unfortunately, less than 20% of PDAC patients are eligible for surgical resection at diagnosis.

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Circulating tumor DNA (ctDNA), a fragment of tumor DNA found in the bloodstream, has emerged as a revolutionary tool in cancer management. This review delves into the biology of ctDNA, examining release mechanisms, including necrosis, apoptosis, and active secretion, all of which offer information about the state and nature of the tumor. Comprehensive DNA profiling has been enabled by methods such as whole genome sequencing and methylation analysis.

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Gastroesophageal cancers (GECs) represent a significant clinical challenge. For early resectable GEC, the integration of immune checkpoint inhibitors into the perioperative chemotherapy and chemoradiation treatment paradigms are being explored and showing promising results. Frontline management of metastatic GEC is exploring the role of targeted therapies beyond PD-1 inhibitors, including anti-human epidermal growth factor receptor 2 agents, Claudin 18.

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Article Synopsis
  • The study evaluates the effectiveness of targeted agents, specifically pertuzumab plus trastuzumab, in patients with advanced biliary tract cancer (BTC) who have specific genomic alterations.
  • Out of 29 enrolled patients, the treatment showed a 40% disease control rate, with some experiencing significant responses, indicating potential benefits of this combination therapy.
  • Although the treatment was generally well-received, a few patients reported notable adverse events, highlighting the importance of monitoring safety alongside treatment efficacy.
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Background: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium.

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Background: The role of systemic therapy in the management of ampullary (AA) and duodenal adenocarcinoma (DA) remains poorly understood. This study sought to synthesize current evidence supporting the use of neoadjuvant therapy (NAT) in AA and DA.

Methods: The study searched PubMed, Cochrane Library (Wiley), Embase (Elsevier), CINAHL (EBSCO), and ClinicalTrials.

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Ampullary cancers refer to tumors originating from the ampulla of Vater (the ampulla, the intraduodenal portion of the bile duct, and the intraduodenal portion of the pancreatic duct), while periampullary cancers may arise from locations encompassing the head of the pancreas, distal bile duct, duodenum, or ampulla of Vater. Ampullary cancers are rare gastrointestinal malignancies, and prognosis varies greatly based on factors such as patient age, TNM classification, differentiation grade, and treatment modality received. Systemic therapy is used in all stages of ampullary cancer, including neoadjuvant therapy, adjuvant therapy, and first-line or subsequent-line therapy for locally advanced, metastatic, and recurrent disease.

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Unlabelled: Since its inception two years ago, the international, multicenter Pancreatic Cancer Early Detection (PRECEDE) Consortium has enrolled high-risk individuals (HRI) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Herein we aim to evaluate enrollment disparities in PRECEDE. Data on HRIs enrolled between May 2020 and March 2022 were collected, with HRIs defined as participants enrolled in PRECEDE meeting guideline-based criteria for PDAC surveillance.

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Cancer alters the function of multiple organs beyond those targeted by metastasis. Here we show that inflammation, fatty liver and dysregulated metabolism are hallmarks of systemically affected livers in mouse models and in patients with extrahepatic metastasis. We identified tumour-derived extracellular vesicles and particles (EVPs) as crucial mediators of cancer-induced hepatic reprogramming, which could be reversed by reducing tumour EVP secretion via depletion of Rab27a.

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Purpose: To develop recommendations involving targeted therapies for patients with advanced gastroesophageal cancer.

Methods: The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.

Results: Eighteen randomized controlled trials met the inclusion criteria for the systematic review.

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Background: The relationship between CINV duration and recurrence in subsequent cycles is largely unstudied. Our objective was to determine if patients experiencing CINV in their first cycle of chemotherapy (C1) would face increased risk of CINV in later cycles and whether the duration of the CINV would predict increased risk of recurrence.

Patients And Methods: Using data from a previously reported phase III trial, we assessed patients' recurrence of breakthrough CINV after antiemetic prophylaxis for anthracycline+cyclophosphamide (AC) for breast cancer, comparing C1 short CINV vs.

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Objectives: To examine glycemic variability within one month and one year following surgery and throughout adjuvant chemotherapy among patients with stage II-III colon cancer, with and without type 2 diabetes (T2D).

Sample & Setting: 58 patients with stage II-III colon cancer treated with surgery and chemotherapy.

Methods & Variables: A retrospective analysis of electronic health record data over one year showed glycemic variability, measured as standard deviation and coefficient of variation.

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Purpose: TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. The results of a cohort of patients with colorectal cancer (CRC) with mutations treated with cobimetinib (C) plus vemurafenib (V) are reported.

Methods: Eligible patients had advanced CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with V600E/D/K/R mutations, and no , , or mutations.

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Purpose: To develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC).

Methods: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.

Results: Five systematic reviews and 10 randomized controlled trials met the systematic review inclusion criteria.

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Cancer mortality is primarily a consequence of its metastatic spread. Here, we report that methionine sulfoxide reductase A (MSRA), which can reduce oxidized methionine residues, acts as a suppressor of pancreatic ductal adenocarcinoma (PDA) metastasis. MSRA expression is decreased in the metastatic tumors of PDA patients, whereas MSRA loss in primary PDA cells promotes migration and invasion.

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Background: Pancreatic ductal adenocarcinoma (PDAC) is a formidable challenge for patients and clinicians.

Objective: To analyze the distribution of 31 different markers in tumor and stromal portions of the tumor microenvironment (TME) and identify immune cell populations to better understand how neoplastic, non-malignant structural, and immune cells, diversify the TME and influence PDAC progression.

Methods: Whole slide imaging (WSI) and cyclic multiplexed-immunofluorescence (MxIF) was used to collect 31 different markers over the course of nine distinctive imaging series of human PDAC samples.

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Article Synopsis
  • Radiation therapy for pancreatic ductal adenocarcinoma (PDAC) often fails due to radioresistance, linked to cholesterol biosynthesis (CBS) and specifically, the enzyme farnesyl diphosphate synthase (FDPS).
  • Inhibition of FDPS using zoledronic acid (Zol) enhanced the effectiveness of radiation therapy and activated immune cells in both human and mouse models.
  • Results showed that targeting FDPS increased radiosensitivity, improved survival rates, and altered immune responses, suggesting Zol as a promising radiosensitizer and immunomodulator for PDAC treatment.
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Objective: To examine glycemic variability within 1 month and 1 year following surgery among adult patients, with and without Type 2 Diabetes (T2D), treated for stage II-III colon cancer.

Method: A retrospective analysis of electronic health record data was conducted. Glycemic variability (i.

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Stereotactic Radiotherapy (SRT) over 5-15 days can be interdigitated without delaying chemotherapy. Bridging chemotherapy may allow for extended intervals to surgery, potentially improving sterilization of surgical margins and overall survival. SRT for pancreatic adenocarcinoma should not be limited to the tumor, and should consider hypofractionated approaches to regional nodes.

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Article Synopsis
  • A systematic review analyzed 60 studies to assess the safety and efficacy of dosing strategies for obese cancer patients, concluding that they can tolerate full doses just like non-obese patients.
  • The recommendations include using full weight-based doses for chemotherapy, immunotherapy, and targeted therapies in obese patients while suggesting that dose adjustments for side effects should be similar to those for non-obese patients; further research on body composition effects is also encouraged.
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Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients' advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer.

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