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Discovery Medicine Jun 2024Atypical acinar cell foci (AACF) seen in pancreatic cancer are fatal and have been studied with some causative agents. However, for the first time, the effect of...
BACKGROUND
Atypical acinar cell foci (AACF) seen in pancreatic cancer are fatal and have been studied with some causative agents. However, for the first time, the effect of acetylsalicylic acid with nitric oxide (NO-ASA) on AACF was examined in this study. Although NO-ASA has very successful inhibitory effects against some types of cancer, it has not been investigated whether they can exert their inhibition effects on AACFs.
METHODS
For experimental purposes, 21 14-day-old male Wistar albino rats were used. Azaserine (30 mg/kg) was dissolved in 0.9% NaCl solution and injected intraperitoneally (i.p.) into 14 rats, except for the Control group (Cont) rats, for three weeks. Rats that were injected with azaserine once a week for three weeks and those that did not receive treatment were divided into experimental groups. 15 days after the end of the azaserine injection protocol, NO-ASA was applied to azaserine with NO-ASA (Az+NO-ASA) group rats three consecutive times with an interval of 15 days by gavage. At the end of the 5-month period, pancreatic tissue was dissected and weighed. Pancreas preparations prepared from histological sections were examined for AACF burden and analyzed via a video image analyzer. One-way analysis of variance (ANOVA) non-parametric statistical analyses were performed to test whether there was a difference between the averages of the experimental and Control groups.
RESULTS
AACF burden in both groups injected with azaserine was found to be statistically significant in all categories compared to that of the Control group ( < 0.05). The average Calculated Estimated average AACF volume (mm) values, the Calculated estimated average AACF diameter (μm), the Estimated average number of AACF per unit volume, AACF rate as a % of Calculated Organ Volume were higher in the AzCont group rats than in the Az+NO-ASA group, when compared, and there was an important level statistical difference between the groups ( < 0.05). It was determined that for all parameters AACFs load in Az+NO-ASA group rats were significantly reduced compared to that of AzCont group rats ( < 0.05).
CONCLUSIONS
We observed that, as a result of the NO-ASA application, the experimental AACF focus ratio created by azaserine injection was significantly inhibited. The inhibitory effect of AACFs in Az+NO-ASA group rats may have resulted from the significant and independent chemopreventive and/or chemotherapeutic activity of NO-ASA against exocrine pancreatic AACF foci.
Topics: Animals; Male; Aspirin; Rats, Wistar; Nitric Oxide; Rats; Pancreatic Neoplasms; Acinar Cells; Pancreas, Exocrine
PubMed: 38926102
DOI: 10.24976/Discov.Med.202436185.106 -
Pancreatology : Official Journal of the... Jun 2024Pancreatic ductal adenocarcinoma (PDAC) with a diameter ≤10 mm and high-grade pancreatic intraepithelial neoplasia (HG-PanIN) require pre-operative diagnosis. Most...
OBJECTIVES
Pancreatic ductal adenocarcinoma (PDAC) with a diameter ≤10 mm and high-grade pancreatic intraepithelial neoplasia (HG-PanIN) require pre-operative diagnosis. Most cases present only indirect imaging findings without visible tumors on endoscopic ultrasound (EUS). Therefore, EUS-guided fine-needle aspiration/biopsy is not applicable. An alternative diagnostic method is pancreatic juice cytology (PJC) via endoscopic naso-pancreatic drainage (ENPD-PJC), which is not the standard practice. This study aimed to investigate ENPD-PJC for diagnosing suspected PDAC/HG-PanIN cases without visible tumors on EUS.
METHODS
Data of patients with suspected PDAC/HG-PanIN without visible tumors who underwent PJC were retrospectively evaluated. One PJC sample was collected during endoscopic retrograde pancreatography (ERP-PJC), and 12 samples were collected during ENPD-PJC, 3-hourly for cytological analysis. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC positivity indicated cytologically positive samples. Patients with positive/negative PJC with follow-up for <4-years were excluded as undiagnosed cases. A non-malignant diagnosis was based on histopathological absence/stable imaging findings for ≥4-years. The primary endpoint was to demonstrate that ERP/ENPD-PJC has a higher diagnostic ability than ERP-PJC.
RESULTS
Twenty-two patients with histopathologically diagnosed PDAC/HG-PanIN and 31 with a non-malignant diagnosis were enrolled. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC showed sensitivities of 36.4 %, 86.4 %, and 77.3 %, specificities of 93.5 %, 87.1 %, and 93.5 %, and accuracies of 69.8 %, 86.7 %, and 86.7 %, respectively. ERP/ENPD-PJC and ENPD-PJC demonstrated superior sensitivity and accuracy compared to ERP-PJC. A greater occurrence of positive outcomes markedly distinguished true positives from false positives.
CONCLUSIONS
ERP/ENPD-PJC and ENPD-PJC had higher diagnostic accuracies for PDAC/HG-PanIN without visible tumors on EUS. ENPD-PJC is recommended for the diagnosis of these lesions.
PubMed: 38926041
DOI: 10.1016/j.pan.2024.06.006 -
Anticancer Research Jul 2024A deep ultraviolet (DUV) light-emitting diode (LED) is a device that can irradiate electromagnetic waves from 250 nm to 350 nm. Tousled-like kinase 1 (TLK1) encodes a...
BACKGROUND/AIM
A deep ultraviolet (DUV) light-emitting diode (LED) is a device that can irradiate electromagnetic waves from 250 nm to 350 nm. Tousled-like kinase 1 (TLK1) encodes a nuclear serine/threonine kinase, which is thought to influence the effects of DUV irradiation in cancer. The aim of this study was to clarify the interaction of TLK1 with DUV irradiation-induced DNA damage in cancer cells.
MATERIALS AND METHODS
Pancreatic cancer cell lines were treated with or without DUV. TLK1 expression and phosphorylation in the two groups were examined. Then, these cancer cell lines were treated with thioridazine (THD), DUV or both. Thereafter, cytomorphology and apoptosis were assessed. Several proteins related to DNA damage, were analyzed in cancer cells treated with DUV and THD. Tumors in a subcutaneous xenograft model were treated with THD, DUV, or both for six weeks.
RESULTS
DUV irradiation induced the phosphorylation of TLK1 in pancreatic cancer cell lines. Cytomorphology was significantly changed in pancreatic cancer cells treated with DUV and THD. TLK1 inhibition enhanced DUV irradiation-induced apoptosis in cancer cells. Interestingly, CHK1 and pCHK1 expression was suppressed after TLK1 inhibition. In addition, inhibition of MRE11 led to a decrease in the expression of CHK1 and pCHK1, accompanied by a notable increase in apoptosis. In the subcutaneous xenograft models, the tumor volume in the DUV and THD groups was lower than that in the other groups.
CONCLUSION
TLK1 phosphorylation is an important event in DUV irradiation. DUV irradiation combined with TLK1 inhibition has therapeutic potential in pancreatic cancer cells.
Topics: Checkpoint Kinase 1; Humans; Animals; Pancreatic Neoplasms; Apoptosis; Protein Serine-Threonine Kinases; Cell Line, Tumor; Xenograft Model Antitumor Assays; Ultraviolet Rays; Phosphorylation; DNA Damage; Mice; Mice, Nude
PubMed: 38925844
DOI: 10.21873/anticanres.17095 -
Anticancer Research Jul 2024Sorafenib and lenvatinib have long been used as a first-line treatment for advanced hepatocellular carcinoma (HCC). Along with the development of systemic chemotherapy...
BACKGROUND/AIM
Sorafenib and lenvatinib have long been used as a first-line treatment for advanced hepatocellular carcinoma (HCC). Along with the development of systemic chemotherapy for HCC, the concept of conversion hepatectomy has recently become widespread. The present study aimed to assess the clinical outcomes of sorafenib and lenvatinib for HCC regarding the possibility of conversion hepatectomy in clinical practice.
PATIENTS AND METHODS
A total of 295 patients with advanced HCC receiving sorafenib and lenvatinib, accounting for 306 treatments (sorafenib, n=157; lenvatinib, n=149, 11 patients received lenvatinib after sorafenib treatment) at five different institutions were enrolled. Patients were assessed for their clinical characteristics and therapeutic response using both Response Evaluation Criteria in Solid Tumors criteria (RECIST) and modified RECIST (mRECIST) criteria. Additionally, an indication of surgery after tyrosine kinase inhibitor administration was determined based on the tumor status of patients.
RESULTS
The median survival times of patients treated with sorafenib and lenvatinib were 12.8 and 16.4 months, respectively, without significant difference (p=0.1645). The objective response rates (ORR) of sorafenib based on mRECIST and RECIST were 10.1% and 5.9%, respectively, and those of lenvatinib were 38.1% and 19.0%, respectively. Among the 306 treatments, two cases (sorafenib and lenvatinib, one each) underwent hepatectomy after systemic chemotherapy.
CONCLUSION
Few cases with unresectable HCC were amenable to conversion hepatectomy after sorafenib and lenvatinib treatments due to the limited ORR by RECIST. Cautious approach must be taken when administering neoadjuvant chemotherapy aimed at conversion hepatectomy.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Quinolines; Phenylurea Compounds; Sorafenib; Male; Female; Hepatectomy; Middle Aged; Aged; Adult; Aged, 80 and over; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Agents
PubMed: 38925835
DOI: 10.21873/anticanres.17123 -
Anticancer Research Jul 2024This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal...
BACKGROUND/AIM
This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal surface malignancies.
PATIENTS AND METHODS
This study retrospectively analyzed a database of 28 patients who had received one cycle of normothermic PIPAC prior to repetitive WBH-PIPACs. WBH (39-40°C) was induced using a Water-filtered infrared A device. Doxorubicin plus cisplatin or oxaliplatin was nebulized into a constant capnoperitoneum of 20 mmHg for 30 min at doses of 6.0 mg, 30.0 mg, or 120 mg per m body surface area, respectively. The primary outcome measures were feasibility and perioperative complications.
RESULTS
The median age was 62 years (range=45-78 years). Primary tumor sites included the upper gastrointestinal tract (n=9), colon/rectum (n=7), hepato-pancreato-biliary system (n=3), peritoneum (n=2), ovaries (n=2), and unknown primary (n=5). The induction of WBH failed in one patient (6 liters ascites). After a median warming period of 95 min (53-117 min), the median rectal temperature (T) was 39.5°C (39.2-39.9°C). No hyperthermia-related side effects were observed. Twenty-seven patients received 50 WBH-PIPACs. The median time of therapeutic capnoperitoneum and treatment time with T ≥39°C was 39 min (37-43 min) and 66 min (53-69 min), respectively. The overall rate of postoperative procedure-related complications was 9/50, including seven grade I and two grade II complications. There were no grade III-V complications.
CONCLUSION
In a highly selected group of patients, the feasibility and perioperative safety of WBH-PIPAC was comparable to normothermic PIPAC.
Topics: Humans; Middle Aged; Female; Aged; Male; Peritoneal Neoplasms; Feasibility Studies; Retrospective Studies; Aerosols; Hyperthermia, Induced; Cisplatin; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols; Hyperthermic Intraperitoneal Chemotherapy; Oxaliplatin
PubMed: 38925817
DOI: 10.21873/anticanres.17117 -
Endoscopy Dec 2024
Topics: Humans; Pancreatic Neoplasms; Endoscopy, Digestive System; Carcinoma, Pancreatic Ductal; Pancreatic Intraductal Neoplasms; Male; Adenocarcinoma, Mucinous; Aged; Female
PubMed: 38925167
DOI: 10.1055/a-2339-2121 -
Cancer Medicine Jun 2024Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore,...
AIM
Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs.
METHODS
This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed.
RESULTS
The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105-0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157-10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin-bilirubin score (HR: 9.083, 95% CI: 1.118-73.76) was associated with bleeding events (p = 0.039).
CONCLUSIONS
DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.
Topics: Humans; Carcinoma, Hepatocellular; Male; Liver Neoplasms; Female; Antibodies, Monoclonal, Humanized; Retrospective Studies; Lung Neoplasms; Aged; Middle Aged; Feasibility Studies; Hemorrhage; Bevacizumab; Antineoplastic Combined Chemotherapy Protocols; Anticoagulants; Administration, Oral; Aged, 80 and over
PubMed: 38924675
DOI: 10.1002/cam4.7430 -
Cancer Medicine Jun 2024Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following...
BACKGROUND
Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions.
METHODS
The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice.
RESULTS
AG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS.
CONCLUSIONS
This study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy.
Topics: Humans; Pancreatic Neoplasms; Gemcitabine; Male; Female; Deoxycytidine; Albumins; Paclitaxel; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Aged; Retrospective Studies; Prognosis; Adult; Aged, 80 and over; Treatment Outcome; Italy; Neoplasm Metastasis
PubMed: 38924262
DOI: 10.1002/cam4.7345 -
Resistance to gemcitabine is mediated by the circ_0036627/miR-145/S100A16 axis in pancreatic cancer.Journal of Cellular and Molecular... Jun 2024The development of gemcitabine (GEM) resistance severely limits the treatment efficacy in pancreatic cancer (PC) and increasing evidence highlights the vital roles of...
The development of gemcitabine (GEM) resistance severely limits the treatment efficacy in pancreatic cancer (PC) and increasing evidence highlights the vital roles of circular RNAs (circRNAs) in the tumorigenesis, progression and drug resistance of PC. However, the circRNAs underlying GEM resistance development of PC remains to be clarified. The current research aims to unveil the roles of circ_0036627 in dictating the aggressiveness and GEM sensitivity in PC. We reported the increased expression of circ_0036627 in PC tissues and PC cell lines. Elevated circ_0036627 expression level was correlated with advanced tumour grade and poor overall survival in PC patients. Functional assays and in vivo experiments demonstrated that circ_0036627 overexpression was required for the proliferation, migration invasion and GEM resistance in PC cells. circ_0036627 knockdown suppressed tumour development in vivo. The molecular analysis further showed that circ_0036627 increased S100A16 expression by sponging microRNA-145 (miR-145), a tumour-suppressive miRNA that could significantly attenuate PC cell proliferation, migration, invasion and GEM resistance. Furthermore, our findings suggested that S100A16 acted as an oncogenic factor to promote aggressiveness and GEM resistance in PC cells. In conclusion, the current findings provide new mechanistic insights into PC aggressiveness and GEM resistance, suggesting the critical role of circ_0036627/miR-145/S100A16 axis in PC progression and drug resistance development and offering novel therapeutic targets for PC therapy.
Topics: Gemcitabine; Deoxycytidine; Humans; Pancreatic Neoplasms; RNA, Circular; Drug Resistance, Neoplasm; MicroRNAs; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Proliferation; Animals; Cell Movement; Male; S100 Proteins; Mice; Female; Mice, Nude; Middle Aged; Antimetabolites, Antineoplastic
PubMed: 38924205
DOI: 10.1111/jcmm.18444 -
PloS One 2024The association between red meat, fish, and processed meat consumption and the risk of developing gastrointestinal (GI) cancers remains inconclusive despite several... (Meta-Analysis)
Meta-Analysis
The association between major gastrointestinal cancers and red and processed meat and fish consumption: A systematic review and meta-analysis of the observational studies.
BACKGROUND
The association between red meat, fish, and processed meat consumption and the risk of developing gastrointestinal (GI) cancers remains inconclusive despite several investigations. Therefore, we conducted a systematic review and meta-analysis of observational studies to update the existing scientific evidence.
METHODS
We searched PubMed, Web of Science, and Scopus databases until May 20, 2023. We analyzed observational studies that examined the associations between red and processed meat and fish consumption and GI cancers. We assessed between-study heterogeneity using the χ2 and τ2 tests, as well as I2 statistics. We explored the likelihood of publication bias using Begg's and Egger's tests and trim-and-fill analysis. We reported the overall effect sizes as odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model.
RESULTS
Of the 21,004 studies identified, 95 studies involving 5,794,219 participants were included in the meta-analysis. The consumption of high levels of red meat, as compared to low levels, was found to significantly increase the risk of developing esophageal, pancreatic, liver, colon, rectal, and colorectal cancers. Similarly, the consumption of high levels of processed meat, as compared to low levels, significantly increased the risk of pancreatic, colon, rectal, and colorectal cancers. In contrast, the consumption of high levels of fish, as compared to low levels, significantly reduced the risk of colon, rectal, and colorectal cancers.
CONCLUSIONS
This meta-analysis provides updated evidence on the association between red meat, processed meat, and fish consumption and the risk of developing five major types of GI cancers.
Topics: Humans; Gastrointestinal Neoplasms; Red Meat; Animals; Observational Studies as Topic; Fishes; Meat Products; Risk Factors; Meat; Seafood; Diet
PubMed: 38924054
DOI: 10.1371/journal.pone.0305994