Programmed death-ligand 1 (PD-L1) expression has now been implicated in gastric cancer (GC). This study was conducted to determine the impact of clinicopathological characteristics on PD-L1 ...expression and its association with survival in GC patients receiving standard-of-care. In total, 268 GC patients receiving upfront surgery were enrolled at Chiang Mai University Hospital. PD-L1 expression was assayed by immunohistochemistry staining using the Dako 22C3 pharmDx. The rates of PD-L1 positivity by combined positive score (CPS) at a cutoff value of 1 and 5 were 22% and 7%. PD-L1 positivity was significantly higher in patients younger than 55 than those older than 55 (32.6% vs. 16.5%, p = 0.003; 11.6% vs. 4.4%, p = 0.027). PD-L1 positivity was observed more frequently in GC with metastases than without (25.2% vs. 17.1%, p = 0.112; 7.2% vs. 6.7%, p = 0.673). Patients with PD-L1 positive had a significantly shorter median overall survival than those with PD-L1 negative (32.7 vs. 41.6 months, p = 0.042, 27.6 vs. 40.8 months, p = 0.038). In conclusion, PD-L1 expression has been associated with young age, short survival, and metastases, although unrelated to the tumor stage. For GC patients, PD-L1 testing is recommended, especially among young patients with metastases.
The incidence of lung cancer has increased while the mortality rate has continued to remain high. Effective treatment of this disease is the key to survival. Therefore, this study is a necessity in ...continuing research into new effective treatments. In this study we determined the effects of three different Thai herbs on lung cancer.
,
, and
were extracted by ethyl acetate and 50% ethanol. The cytotoxicity was tested with A549 lung cancer cell line. We found four effective extracts that exhibited toxic effects on A549 cells. These extracts included ethyl acetate extracts of
(BEA),
(CEA), and
(EEA), and an ethanolic extract of
(EE). Moreover, these effective extracts were tested in combination with chemotherapeutic drugs. An effective synergism of these treatments was found specifically through a combination of BEA with methotrexate, EE with methotrexate, and EE with etoposide. Apoptotic cell death was induced in A549 cells by these effective extracts via the mitochondria-mediated pathway. Additionally, we established primary lung cancer and normal epithelial cells from lung tissue of lung cancer patients. The cytotoxicity results showed that EE had significant potential to be used for lung cancer treatment. In conclusion, the four effective extracts possessed anticancer effects on lung cancer. The most effective extract was found to be
(EE).
In Southeast Asia, the rhizome of Etlingera pavieana is commonly consumed and parts of the rhizomes have been used as a medicine for the treatment of several disorders. Its pharmacological effects ...have previously been reported. However, its potential toxicity has not been described. This study aimed to evaluate in vivo toxicity of E. pavieana rhizome extract (EPE) in Sprague Dawley rats. Acute toxicity testing of EPE at a single dose of 2,000 mg/kg produced no toxic effects in female rats after 14 days of treatment. Subchronic toxicity testing showed that all doses of EPE (500, 1,000, and 2,000 mg/kg/day) produced no sign of toxicity during 90 days of treatment. All biochemical and hematological values were within normal ranges. There were no significant histopathological differences in the internal organs among the tested groups. Therefore, the no-observed-adverse-effect level of EPE was 2,000 mg/kg/day in both male and female rats, thereby confirming the safety of EPE for use in traditional medicines.
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•Evaluating the acute and subchronic oral toxicity of Etlingera pavieana rhizome extract (EPE) in rats.•EPE at tested doses did not produce any signs of acute and 90-day oral toxicity.•The NOAEL of EPE can be considered to be higher than 2,000 mg/kg/day.•The safety of E. pavieana rhizomes in rats provides support for the use as food and in medicines.
Primary liver cancer (PLC), which includes intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC), has the highest incidence of all cancer types in Thailand. Known etiological ...factors, such as viral hepatitis and chronic liver disease do not fully account for the country's unusually high incidence. However, the gut-liver axis, which contributes to carcinogenesis and disease progression, is influenced by the gut microbiome. To investigate this relationship, fecal matter from 44 Thai PLC patients and 76 healthy controls were subjected to whole-genome metagenomic shotgun sequencing and then analyzed by marker gene-based and assembly based methods. Results revealed greater gut microbiome heterogeneity in iCCA compared to HCC and healthy controls. Two Veillonella species were found to be more abundant in iCCA samples and could distinguish iCCA from HCC and healthy controls. Conversely, Ruminococcus gnavus was depleted in iCCA patients and could distinguish HCC from iCCA samples. High Veillonella genus counts in the iCCA group were associated with enriched amino acid biosynthesis and glycolysis pathways, while enriched phospholipid and thiamine metabolism pathways characterized the HCC group with high Blautia genus counts. These findings reveal distinct landscapes of gut dysbiosis among Thai iCCA and HCC patients and warrant further investigation as potential biomarkers.
We report a case of conjunctival intraepithelial neoplasia (CIN) in a patient presenting with the pigmented conjunctival lesion.This study involved a 56-year-old woman that presented with right eye ...irritation for 1 month. She noticed brownish pigmentation arising from her right nasal conjunctiva and growing slowly over time. Biomicroscopic examination showed a gelatinous pigmented conjunctival mass with feeder vessels. Conjunctival impression cytology (CIC) was done and reported as CIN. Treatment was started with 0.02% mitomycin-C eye drops. The conjunctival lesion responded well to medication. This report shows that CIN can manifest as a pigmented tumor, resembling melanoma. CIC plays a role in the diagnosis of this condition. This tumor responded well with 0.02% mitomycin-C eye drops.
This study aimed to investigate the expression of programmed cell death-ligand 1 (PD-L1) and its associations with human papillomavirus (HPV) 16/18 DNA status, p16 expression, demographic, ...clinicopathologic and risk parameters in patients with oral squamous cell carcinoma (OSCC).
A total of 85 formalin-fixed, paraffin-embedded OSCC specimens were collected. HPV16/18 DNA was detected by polymerase chain reaction. PD-L1 and p16 expressions were assessed using immunohistochemical technique. The immunostaining scores were calculated by combined positive score (CPS), previously described. The positive scoring value was determined at CPS ≥1, recommended by FDA. The associations between PD-L1 expression and HPV16/18 DNA status, p16 expression, demographic, clinicopathologic, and risk parameters were analyzed by Chi-square, Fisher's exact tests, and multivariate logistic regression.
PD-L1 expression was detected in 22 out of 85 cases of OSCC (25.9%). 16.5% of all cases were HPV 16/18-positive and 62.4% were p16-positive. Statistically, there were no significant associations between PD-L1 expression in OSCC and HPV16/18 DNA status, p16 expression, demographic and, clinicopathologic parameters or risk behaviors.
Approximately one-fourth of OSCC cases were PD-L1-positive, suggesting candidacy for anti-PD-L1 immunotherapy. Furthermore, HPV infection and p16 expression were not involved with PD-L1 expression. Further clinical trials warrant the benefits of immunotherapy in patients with PD-L1-positive OSCC.
Human papillomavirus; Oral squamous cell carcinoma; PD-L1; p16.
In Thai traditional medicine, Pikad Tri-phol-sa-mut-than has long been used to alleviate gastrointestinal symptoms, renal disease, inflammation-related disorders, and severe malady. This recipe is ...composed of dried fruits of Morinda citrifolia L., Coriandrum sativum L., and Aegle marmelos (L.) Corrêa. The aim of this study was to assess the anti-gastric ulcer property of the water extract of Pikad Tri-phol-sa-mut-than (TS), using various animal models with different inducers, including restraint water immersion stress, indomethacin, and ethanol/hydrochloric acid (EtOH/HCl). Its mechanisms of anti-gastric ulcer actions were also elucidated using both in vitro and in vivo experiments. When compared with the control groups, the oral pretreatment of TS at the doses of 150, 300 and 600 mg/kg significantly reduced the gastric ulcer formation in all models. It was also found that TS at the dose of 600 mg/kg could increase gastric wall mucus in rats but could not produce the significant reduction of the gastric volume or total acidity of gastric content. Results from hematoxylin and eosin (H&E) and Periodic acid-Schiff (PAS) staining examinations of gastric tissues confirmed that TS visibly reduced gastric mucosal damage, while immunohistochemistry revealed that TS remarkably suppressed the protein expression of Bcl-2-associated X (BAX), a regulator of apoptosis, compared to those of the control group. The DPPH, ABTS, and FRAP assays showed antioxidant effects of TS. All of these findings demonstrated that TS has gastroprotective effects, which may be related to the increase in the gastric wall mucus secretion, not anti-secretory activity, as well as its antioxidant and antiapoptotic activities.
Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is ...hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process.
An appropriate treatment of older lung cancer patients has become an important issue. The aim of this study is to evaluate the short and long-term surgical outcomes in lung cancer patients using 70 ...years as a cut-point, and to identify prognostic factors of cancer-specific mortality in patients older than 70 years.
Medical records of non-small cell lung cancer (NSCLC) patients who underwent pulmonary resection at Chiang Mai University Hospital from January 2002 through December 2016 were retrospectively reviewed. Patients were divided into age less than 70 years (control group) and 70 years or more (study group). Primary outcomes were major post-operative complications and in-hospital death (POM); secondary outcome was long-term survival. Multivariable regression analysis was used.
This study included 583 patients, 167 for study group, and 416 for control group. There were no differences in POM, both at univariable and multivariable analyses, however, for long-term cancer-specific mortality, the study group was more likely to die (HRadj = 1.40, 95%CI = 1.03–1.89). Adverse prognostic factors for long-term mortality in study group were having universal coverage scheme (HRadj = 1.70, 95%CI = 1.03–2.79), the presence of intratumoral lymphatic invasion (HRadj = 2.83, 95%CI = 1.28–6.29), perineural invasion (HRadj = 2.80, 95%CI = 1.13–6.94), underwent lymph node sampling (HRadj = 2.23, 95%CI = 1.16–4.30) and higher stage of disease (HRadj = 2.02, 95%CI = 1.06–3.85 for stage III, HRadj = 3.40, 95%CI = 1.29–8.94 for stage IV).
In-hospital mortality and composite post-operative complications are acceptable in pulmonary resection for NSCLC patients older than 70 years. However, these patients had shorter long-term survival, especially who have some adverse prognostic factors. Further studies with larger sample size are warranted.
Objective:
The operating procedure of a resternotomy in open-heart surgery is a complicated procedure with potentially problematic outcomes partly due to potential adhesions in the pericardial cavity ...and retrosternal space. Use of a collagen membrane has shown encouraging results in adhesion prevention in several regions of the body. This study was designed to evaluate the effectiveness of the use of this collagen membrane in the prevention of pericardial adhesions.
Materials and methods:
A total of 12 pigs were divided randomly into 2 groups: an experimental group in which collagen membranes were used and a control group. After sternotomy and an anterior pericardiectomy, the epicardial surface was exposed to room air and irrigated with saline, and an epicardial abrasion was performed using a sponge. The pericardial defect was repaired using a collagen membrane in the experimental group or left uncovered in the control group. After 8 to 12 weeks, the pigs were killed, and a resternotomy was performed by a single-blinded surgeon enabling the evaluation of adhesions. The heart was then removed and sent for microscopic assessment conducted by a single-blinded pathologist.
Results:
The resternotomy operations performed using a collagen membrane demonstrated a nonstatistically significant trend of fewer macroscopic and microscopic adhesions in all regions (P > .05), particularly in the retrosternal and defect regions.
Conclusions:
This study showed nonstatistically significant differences between the outcomes in the collagen membrane group and the control group in both macroscopic and microscopic adhesion prevention. Due to the many limitations in animal study design, further studies in human models will be needed before the true value of this procedure can be evaluated.
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