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Journal of Biochemical and Molecular... Jun 2024The aim of this investigation was to evaluate the differential expression of the sterol O-acyltransferase 1 (SOAT1) protein in gallbladder cancer tissues and cells,...
The aim of this investigation was to evaluate the differential expression of the sterol O-acyltransferase 1 (SOAT1) protein in gallbladder cancer tissues and cells, investigate the impact of Avastin on the proliferation, migration, invasion capabilities of gallbladder cancer cells, and its potential to induce cell apoptosis. Immunohistochemical analysis of samples from 145 gallbladder cancer patients was conducted, along with analysis of SOAT1 protein, mRNA expression levels, and cholesterol content in gallbladder cancer cell lines SGC-996, NOZ, and gallbladder cancer (GBC)-SD using Western blot and q-PCR techniques. Furthermore, the effects of Avastin on the proliferation, migration, and invasion capabilities of these gallbladder cancer cell lines were studied, and its ability to induce cell apoptosis was evaluated using flow cytometry, Western blot, and immunohistochemical methods. Additionally, gene expression and pathway analysis were performed, and the synergistic therapeutic effects of Avastin combined with gemcitabine were tested in a gallbladder cancer xenograft model. The study found that SOAT1 expression was significantly upregulated in GBC tissues and positively correlated with lymph node metastasis and TNM staging. In vitro experiments demonstrated that Avastin significantly inhibited the proliferation, migration, and invasion capabilities of SGC-996 and GBC-SD cell lines and induced apoptosis. RNA sequencing analysis revealed multiple differentially expressed genes in cells treated with Avastin, primarily enriched in biological pathways such as signaling transduction, malignant tumors, and the immune system. In vivo, experiments confirmed that Avastin could effectively suppress tumor growth in a gallbladder cancer xenograft model and enhanced the treatment efficacy when used in combination with gemcitabine. Overall, these findings provide new insights and strategies for targeted therapy in gallbladder cancer.
Topics: Gallbladder Neoplasms; Humans; Female; Male; Cell Line, Tumor; Animals; Middle Aged; Sterol O-Acyltransferase; Mice; Gemcitabine; Cell Proliferation; Antibodies, Monoclonal, Humanized; Mice, Nude; Apoptosis; Deoxycytidine; Cell Movement; Xenograft Model Antitumor Assays; Aged; Gene Expression Regulation, Neoplastic; Mice, Inbred BALB C; Neoplasm Proteins
PubMed: 38770938
DOI: 10.1002/jbt.23733 -
BMC Gastroenterology May 2024Endoscopic biliary stenting (EBS) is commonly used for preoperative drainage of localized perihilar cholangiocarcinoma (LPHC). This study retrospectively compared the... (Comparative Study)
Comparative Study
BACKGROUND/PURPOSE
Endoscopic biliary stenting (EBS) is commonly used for preoperative drainage of localized perihilar cholangiocarcinoma (LPHC). This study retrospectively compared the utility of inside stent (IS) and conventional stent (CS) for preoperative EBS in patients with LPHC.
METHODS
EBS was performed in 56 patients with LPHC. EBS involved the placement of a CS (n = 32) or IS (n = 24). Treatment outcomes were compared between these two groups.
RESULTS
Preoperative recurrent biliary obstruction (RBO) occurred in 23 patients (71.9%) in the CS group and 7 (29.2%) in the IS group, with a significant difference (p = 0.002). The time to RBO (TRBO) was significantly longer in IS than in CS (log-rank: p < 0.001). The number of stent replacements was significantly lower in IS than CS [0.38 (0-3) vs. 1.88 (0-8), respectively; p < 0.001]. Gemcitabine-based neoadjuvant chemotherapy (NAC) was administered to 26 patients (46.4%). Among patients who received NAC, TRBO was longer in IS than in CS group (log-rank: p < 0.001). The IS group had a significantly shorter preoperative and postoperative hospital stay than the CS group (20.0 vs. 37.0 days; p = 0.024, and 33.5 vs. 41.5 days; p = 0.016). Both the preoperative and the postoperative costs were significantly lower in the IS group than in the CS group (p = 0.049 and p = 0.0034, respectively).
CONCLUSION
Compared with CS, IS for preoperative EBS in LPHC patients resulted in fewer complications and lower re-intervention rates. The fact that the IS group had shorter preoperative and postoperative hospital stays and lower costs both preoperatively and postoperatively compared to the CS group may suggest that the use of IS has the potential to benefit not only the patient but also the healthcare system.
Topics: Humans; Male; Stents; Female; Drainage; Bile Duct Neoplasms; Retrospective Studies; Middle Aged; Aged; Klatskin Tumor; Preoperative Care; Cholestasis; Neoadjuvant Therapy; Deoxycytidine; Gemcitabine; Recurrence; Treatment Outcome; Aged, 80 and over; Adult
PubMed: 38769494
DOI: 10.1186/s12876-024-03266-z -
Gene Sep 2024Cordyceps militaris is a medicinal entomopathogenic fungus containing valuable biometabolites for pharmaceutical applications. Its genetic inheritance and environmental...
Cordyceps militaris is a medicinal entomopathogenic fungus containing valuable biometabolites for pharmaceutical applications. Its genetic inheritance and environmental factors play a crucial role in the production of biomass enriched with cordycepin. While temperature is a crucial controlled parameter for fungal cultivation, its impacts on growth and metabolite biosynthesis remains poorly characterized. This study aimed to investigate the metabolic responses and cordycepin production of C. militaris strain TBRC6039 under various temperature conditions through transcriptome analysis. Among 9599 expressed genes, 576 genes were significantly differentially expressed at culture temperatures of 15 and 25 °C. The changes in the transcriptional responses induced by these temperatures were found in several metabolisms involved in nutrient assimilation and energy source, including amino acids metabolism (e.g., glycine, serine and threonine metabolism) and lipid metabolism (e.g., biosynthesis of unsaturated fatty acids and steroid biosynthesis). At the lower temperature (15 °C), the biosynthetic pathways of lipids, specifically ergosterol and squalene, were the target for maintaining membrane function by transcriptional upregulation. Our study revealed the responsive mechanisms of C. militaris in acclimatization to temperature conditions that provide an insight on physiological manipulation for the production of metabolites by C. militaris.
Topics: Cordyceps; Temperature; Transcriptome; Lipid Metabolism; Acclimatization; Deoxyadenosines; Fatty Acids; Gene Expression Profiling; Genes, Fungal
PubMed: 38768876
DOI: 10.1016/j.gene.2024.148574 -
Chemosphere Jul 2024Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals linked to adverse pregnancy outcomes. Although their underlying biological mechanisms are not fully...
BACKGROUND
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals linked to adverse pregnancy outcomes. Although their underlying biological mechanisms are not fully understood, evidence suggests PFAS may disrupt endocrine functions and contribute to oxidative stress (OS) and inflammation.
OBJECTIVE
We examined associations between early pregnancy PFAS exposure and OS biomarkers, exploring potential effect modifications by fetal sex and maternal race.
METHODS
We used data from 469 LIFECODES participants with measured plasma PFAS (median 10 weeks gestation) and repeated measures (median 10, 18, 26, and 35 weeks gestation) of urinary OS biomarkers [8-iso-prostaglandin-F2α (8-isoprostane) and 8-hydroxydeoxyguanosine (8-OHdG)]. Protein damage biomarkers (chlorotyrosine, dityrosine, and nitrotyrosine) were additionally measured in plasma from a subset (N = 167) during the third visit. Associations between each PFAS and OS biomarkers were examined using linear mixed-effects models and multivariable linear regressions, adjusting for potential confounders, including maternal age, race, education level, pre-pregnancy BMI, insurance status, and parity. Effect modifications were evaluated by including an interaction term between each PFAS and fetal sex or maternal race in the models.
RESULTS
We observed significant positive associations between PFOS and 8-isoprostane, with a 9.68% increase in 8-isoprostane levels (95% CI: 0.10%, 20.18%) per interquartile range increase in PFOS. In contrast, PFUA was negatively associated [9.32% (95% CI: -17.68%, -0.11%)], while there were suggestive positive associations for MPAH and PFOA with 8-isoprostane. The associations of several PFAS with 8-OHdG varied by fetal sex, showing generally positive trends in women who delivered females, but negative or null in those who delivered males. No significant effect modification by maternal race was observed.
CONCLUSIONS
This study provides evidence linking PFAS exposure to OS during pregnancy, with potential sex-specific effects of certain PFAS on 8-OHdG. Further research should explore additional OS/inflammatory biomarkers and assess the modifying effects of dietary and behavioral patterns across diverse populations.
Topics: Humans; Female; Fluorocarbons; Oxidative Stress; Pregnancy; Adult; Maternal Exposure; Biomarkers; Environmental Pollutants; Dinoprost; 8-Hydroxy-2'-Deoxyguanosine; Male; Young Adult; Alkanesulfonic Acids
PubMed: 38768789
DOI: 10.1016/j.chemosphere.2024.142363 -
Pancreas Jul 2024To clarify the treatment reality of pancreatic cancer in Japan, focusing on treatment duration and time to death.
OBJECTIVES
To clarify the treatment reality of pancreatic cancer in Japan, focusing on treatment duration and time to death.
MATERIALS AND METHODS
We retrospectively analyzed Japanese hospital claims data for patients diagnosed with pancreatic cancer between April 2009 and October 2018 to investigate treatment patterns, duration of first-line chemotherapy, and time to death.
RESULTS
Of 81,185 eligible patients, 54.2% were male, the mean age was 71.7 years, and 23.3% (n = 18,884) received chemotherapy as primary treatment. The median treatment duration was 14.1 weeks for the 6.7% of patients who received oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX; recommended first-line regimen) and 16.9 weeks for the 30.2% of patients who received gemcitabine plus nab-paclitaxel (GEM + nab-PTX). Time to death for patients who received FOLFIRINOX or GEM + nab-PTX was similar (15.4 and 14.8 months, respectively). The duration of first-line chemotherapy regimens tended to increase annually for both regimens. The time to death for all first-line chemotherapy regimens also increased annually.
CONCLUSIONS
This study revealed the treatment reality of pancreatic cancer in the real-world Japanese setting. Treatment duration and time to death tended to increase over time and did not differ numerically between FOLFIRINOX and GEM + nab-PTX.
Topics: Humans; Pancreatic Neoplasms; Male; Female; Japan; Aged; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Middle Aged; Databases, Factual; Fluorouracil; Irinotecan; Oxaliplatin; Paclitaxel; Gemcitabine; Duration of Therapy; Deoxycytidine; Time Factors; Aged, 80 and over; Albumins; East Asian People
PubMed: 38767967
DOI: 10.1097/MPA.0000000000002321 -
Journal of Investigative Medicine High... 2024The association between Hairy Cell Leukemia (HCL) and non-tuberculous mycobacterial infections (NTMs) is well described, most notably . The exact pathophysiology is not... (Review)
Review
The association between Hairy Cell Leukemia (HCL) and non-tuberculous mycobacterial infections (NTMs) is well described, most notably . The exact pathophysiology is not known. We report a case of a 31-year-old male with concomitantly diagnosed HCL and disseminated infection who presented with rash, pancytopenia, and bulky axillary lymphadenopathy. The was initially diagnosed through use of cell-free DNA detection and confirmed by bone marrow and lymph node cultures. Hairy Cell Leukemia was diagnosed with peripheral flow cytometry and confirmed via the same bone marrow sample. His HCL was put into remission with a single course of cladribine and rituximab chemotherapy; however, his infection persisted for 6 months despite aggressive antimicrobial and surgical therapy. It was finally controlled using high-dose rifampin in combination with azithromycin and ethambutol. This case highlights the known link between HCL and Furthermore, it hints at potential causes beyond chemotherapy-induced immunocompromise. Notable possibilities include HCL cells acting as sanctuary sites for to evade the immune system, and subclinical infections causing NLRP3 inflammasome overactivation to trigger the oncogenic transformation to HCL. More research into the pathophysiologic link between HCL and infections would allow for more effective prevention, diagnosis, and treatment of these severe atypical infections which are the major cause of morbidity in the cladribine era of HCL treatment.
Topics: Humans; Male; Leukemia, Hairy Cell; Adult; Mycobacterium Infections, Nontuberculous; Mycobacterium kansasii; Cladribine; Rifampin; Azithromycin; Rituximab
PubMed: 38767131
DOI: 10.1177/23247096241253343 -
Pakistan Journal of Pharmaceutical... Mar 2024Induction followed by concurrent chemoradiation (CCRT) is the standard of care for locally advanced nasopharyngeal carcinoma (LANPC). This study evaluated and compared... (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparison of efficacy of neoadjuvant chemotherapy with gemcitabine plus cisplatin versus docetaxil, cisplatin, plus fluorouracil in locally advanced nasopharyngeal carcinoma.
Induction followed by concurrent chemoradiation (CCRT) is the standard of care for locally advanced nasopharyngeal carcinoma (LANPC). This study evaluated and compared the efficacy of two regimens of neoadjuvant chemotherapy along with CCRT in LANPC. Patients with LANPC were randomly divided in Group I (receiving neoadjuvant gemcitabine and cisplatin) and Group II (receiving neoadjuvant docetaxil, cisplatin and fluorouracil). Both groups also received concurrent single agent (i.e., cisplatin) chemotherapy and radiotherapy (70Gy). Treatment response was assessed at 8 weeks after the completion of CCRT using RECIST criteria. A total of 68 LANPC patients were enrolled. Group I comprised of 32 patients, with male to female ratio of 2.2, a mean (range, median) age of 38.6±11.3 (19-58, 36) years. Group II comprised of 36 patients, with male to female ratio of 3.5, mean (range, median) age of 40.9 ±11.6 (17-63, 40) years. The complete response was higher whereas the partial response was lower in Group I as compared to Group II (23/32 versus 16/36 and 06/32 versus 18/36, respectively). LANPC patients receiving gemcitabine plus cisplatin based neoadjuvant chemotherapy showed higher response, as compared with docetaxil, cisplatin and fluorouracil based neoadjuvant chemotherapy.
Topics: Humans; Male; Female; Cisplatin; Adult; Gemcitabine; Middle Aged; Fluorouracil; Neoadjuvant Therapy; Deoxycytidine; Antineoplastic Combined Chemotherapy Protocols; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Young Adult; Treatment Outcome; Adolescent
PubMed: 38767105
DOI: No ID Found -
Pakistan Journal of Pharmaceutical... Mar 2024The efficacy of 400mg efavirenz (EFV) once daily is reported to be similar to that of 600mg EFV. However, EFV-related toxic and side effects of 400mg EFV are...
The efficacy of 400mg efavirenz (EFV) once daily is reported to be similar to that of 600mg EFV. However, EFV-related toxic and side effects of 400mg EFV are significantly reduced. Here, the feasibility of reducing EFV to 400mg once a day in HIV-infected/AIDS patients was evaluated. Fifty patients were included. Patients were given 3TC+TDF+400mg EFV (n=25) or 3TC+TDF+600mg EFV (n=25). The proportion of patients with HIV RNA < 40 copies/mL and the adverse events served as the primary and secondary outcomes, respectively. HIV inhibition rates of the 3TC+TDF+400mg EFV group and 3TC+TDF+600mg EFV group were both 56.52% at week 24 and respectively 100%, 91.3% at week 48. During 48 weeks, 27 cases of adverse events were reported in the 3TC+TDF+400mg EFV group, lower than those in the 3TC+TDF+600mg EFV group, which had 39 cases. Compared with the 3TC+TDF+400mg EFV group, the incidence of transaminase, dizziness, hyperlipidemia and rashes all increased in the 3TC+TDF+600mg EFV group (P>0.05). No serious adverse events of the central nervous system occurred. The incidence of depression, sleep disturbance, and vertigo were similar (P>0.05). The efficacy of 400mg EFV is comparable to 600mg EFV. However, patients receiving 400mg EFV have fewer adverse events.
Topics: Humans; Benzoxazines; Cyclopropanes; Alkynes; Male; Female; Adult; Anti-HIV Agents; HIV Infections; Middle Aged; Treatment Outcome; Lamivudine; Tenofovir; Drug Therapy, Combination; Viral Load; RNA, Viral; Acquired Immunodeficiency Syndrome
PubMed: 38767104
DOI: No ID Found -
Neoplasma Jun 2024Pancreatic cancer (PAAD) is a fatal malignancy with a poor prognosis. The treatment strategies are quite limited and gemcitabine is the canonical one, which has been...
Pancreatic cancer (PAAD) is a fatal malignancy with a poor prognosis. The treatment strategies are quite limited and gemcitabine is the canonical one, which has been proven to improve the prognosis of PAAD patients. However, the treatment efficiency of gemcitabine is far from satisfactory and remains to be further improved. DEAD-Box Helicase 46 (DDX46) is a kind of RNA helicase, which promotes multiple cancers development. However, its role in PAAD is largely unknown. In the present study, we found DDX46 was highly expressed in PAAD tissues and correlated with poor prognosis. Knockdown of DDX46 repressed PAAD cell growth in vitro and in vivo and sensitized PAAD cells to gemcitabine treatment. Mechanically, DDX46 bound to JMJD6 and promoted JMJD6/CDK4 signaling pathway. Overexpression of JMJD6 reversed the anti-tumor function of DDX46 knockdown. Our study found a novel pathological mechanism of PAAD progression and provided a potential therapeutic target to improve gemcitabine efficiency.
Topics: Humans; Deoxycytidine; Pancreatic Neoplasms; Gemcitabine; Jumonji Domain-Containing Histone Demethylases; DEAD-box RNA Helicases; Signal Transduction; Drug Resistance, Neoplasm; Cell Line, Tumor; Cyclin-Dependent Kinase 4; Animals; Mice; Cell Proliferation; Prognosis; Antimetabolites, Antineoplastic; Male; Gene Expression Regulation, Neoplastic
PubMed: 38764294
DOI: 10.4149/neo_2024_230904N469 -
Clinical Therapeutics May 2024The case of a 47-year-old female patient who underwent sigmoidectomy for metastatic colorectal cancer is reported. Treatment with capecitabine and 5-fluorouracil induced...
PURPOSE
The case of a 47-year-old female patient who underwent sigmoidectomy for metastatic colorectal cancer is reported. Treatment with capecitabine and 5-fluorouracil induced severe hypertriglyceridemia repeatedly.
METHODS
Based on laboratory tests and clinical evaluations, treatment was suggested by specialists.
FINDINGS
After treatment with capecitabine, the patient's triglycerides increased from 19.7 mmol/L to 42 mmol/L. It was proposed that the patient had multifactorial chylomicronemia syndrome triggered by secondary factors. Statins, fenofibrate, ezetimib, and metformin were added to the therapy. After metastases appeared, FOLFIRI (leucovorin calcium [folinic acid], 5-fluorouracil, and irinotecan hydrochloride) chemotherapy and biological treatment (cetuximab) followed and triglycerides increased to 55.3 mmol/L.
IMPLICATIONS
Monitoring triglyceride levels before and during therapy is suggested.
Topics: Humans; Female; Middle Aged; Fluorouracil; Hypertriglyceridemia; Colorectal Neoplasms; Capecitabine; Antineoplastic Combined Chemotherapy Protocols; Antimetabolites, Antineoplastic; Triglycerides; Leucovorin
PubMed: 38763818
DOI: 10.1016/j.clinthera.2024.05.001