MMT appears to convey longer survival in ATC among patients with stage IVA/B disease.

Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components.

Background. Cancer anorexia-cachexia syndrome (CAS) is a significant comorbidity among all patients with cancer, increasing the mortality rate. Almost all patients with head and neck cancer experience this syndrome. CAS causes increased energy expenditure by increasing systemic inflammation and decreasing energy consumption due to anorexia. It leads to skeleton muscle breakdown and reduces the quality of life. Nutritional interventions and primary cancer treatment are the mainstays to manage this situation. However, a vicious cycle causes CAS to persist, especially in head and neck cancer, where tumour location and its treatment interfere with nutritional interventions. Curcumin shows anti-inflammatory effects, including modulated CAS in animal and in vitro studies. Objective. The study aimed to determine the effect of curcumin to treat cancer anorexia-cachexia syndrome among current patients with locally advanced or advanced head and neck cancer. Methods. This constitutes a randomised, double-blind, placebo-controlled phase IIa study. Twenty patients with CAS in locally advanced or advanced head and neck cancer adequately nourished via a feeding tube were enrolled and randomised in a 1 : 1 ratio to receive oral curcumin (at a dose of 4000 mg daily) (n = 10) or placebo (n = 10) for 8 weeks. The primary endpoint was body composition (muscle mass, body fat mass, and basal metabolic rate). The secondary endpoints were handgrip muscle strength, body mass index, absolute lymphocyte count, and safety and toxicity. Result. There was a statistically significant benefit from curcumin on improving muscle mass compared with placebo (2.16% [95% confidence interval; CI, −0.75 to 5.07] vs. −3.82% [95% CI, −8.2 to 0.57]; P = 0.019 ). The other parameters of body composition were not significant but tended to favour curcumin benefit. The body fat mass (−0.51 [95% CI, −21.89 to 20.86] vs. −8.97% [95% CI, −19.43 to 1.49]; P = 0.432 ) and percentage of mean change in the basal metabolic rate were noted (BMR) (0.54% [95% CI, −1.6 to 2.67] vs. −1.61% [95% CI, −4.05 to 0.84]; P = 0.153 ). Notably, patients treated with curcumin exhibited less reduction in handgrip muscle strength and absolute lymphocyte count but was not significant. Similarly, most adverse events were grade 1 in both groups. Conclusion. The curcumin add-on resulted in a significant increase in muscle mass than standard nutritional support. Furthermore, it may improve and delay a decrease in the other body composition parameters, handgrip strength, and absolute lymphocyte count. Curcumin was safe and well tolerated. This constitutes an unmet need for clinical trials. This trial is registered with NCT04208334.

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Colorectal cancer (CRC) is a major cause of cancer mortality. Currently used CRC biomarkers provide insufficient sensitivity and specificity; therefore, novel biomarkers are needed to improve the CRC detection. Label-free quantitative proteomics were used to identify and compare glycoproteins, enriched by wheat germ agglutinin, from plasma of CRC patients and age-matched healthy controls. Among 189 identified glycoproteins, the levels of 7 and 15 glycoproteins were significantly altered in the non-metastatic and metastatic CRC groups, respectively. Protein-protein interaction analysis revealed that they were predominantly involved in immune responses, complement pathways, wound healing and coagulation. Of these, the levels of complement C9 (C9) was increased and fibronectin (FN1) was decreased in both CRC states in comparison to those of the healthy controls. Moreover, their levels detected by immunoblotting were validated in another independent cohort and the results were consistent with in the study cohort. Combination of CEA, a commercial CRC biomarker, with C9 and FN1 showed better diagnostic performance. Interestingly, predominant glycoforms associated with acetylneuraminic acid were obviously detected in alpha-2 macroglobulin, haptoglobin, alpha-1-acid glycoprotein 1, and complement C4-A of CRC patient groups. This glycoproteomic approach provides invaluable information of plasma proteome profiles of CRC patients and identification of CRC biomarker candidates.

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BACKGROUND Even in the immuno-oncology era, transcatheter arterial chemoembolisation (TACE) is the most effective way to treat intermediate stage hepatocellular carcinoma (HCC). Postembolisation syndrome (PES) is the most common side effect from TACE and there is still no standard prevention guideline. AIM To evaluate the efficacy of single dose intravenous dexamethasone regimen to prevent PES after TACE among patients with HCC. METHODS This study enrolled patients with HCC who had eligible indication for TACE without macrovascular invasion/extrahepatic metastasis. Patients were randomly assigned to either an intravenous single dose of dexamethasone 8 mg or placebo one hour before TACE. The primary outcome was a negative result of PES at 48 h after TACE, which was defined as score < 2 of Southwest Oncology Group toxicity coding criteria using fever, nausea, vomiting and pain to calculated. And the secondary end point was duration of admission between two groups. RESULTS One hundred patients were randomly assigned 1:1. Under intention-to-treat analysis, 49 patients were randomly assigned to the dexamethasone and 51 to the placebo groups. Both groups were similar for baseline characteristics. The negative PES rate was significantly higher in the dexamethasone group than in the placebo group (63.3% vs 29.4%; P = 0.005). Mean Southwest Oncology Group toxicity coding PES was 2.14 (95%CI: 1.41-2.8) vs 3.71 (95%CI: 2.97-4.45) between the dexamethasone and placebo groups, respectively. Cumulative incidence of fever was significantly lower in dexamethasone group with P < 0.001, pain, nausea and vomiting were also lower in the dexamethasone group compared with the placebo group ( P = 0.16, P = 0.11, and P = 0.49). The dexamethasone regimen was generally well tolerated by patients with HCC patients including those with hepatitis B virus infection and well-controlled diabetes mellitus. CONCLUSION Single dose dexamethasone was effective at preventing PES among patients with HCC treated with TACE. The study showed no adverse events of special interest related to dexamethasone.

PURPOSE Atezolizumab plus bevacizumab treatment is a first-line therapy for unresectable hepatocellular carcinoma (HCC) worldwide. The efficacy, safety, and patient-reported outcomes (PROs) of HCC in Thailand have not yet been reported. This study aimed to evaluate the efficacy, safety, and PROs of atezolizumab plus bevacizumab. MATERIALS AND METHODS From September 2020 to August 2021, 30 patients with unresectable HCC who met the inclusion criteria of atezolizumab plus bevacizumab as first-line treatment were enrolled. Analysis was assessed for progression-free survival, overall survival, adverse events (AEs), and quality of life (QoL). RESULTS The median progression-free survival and overall survival periods were 6.7 and 10.2 months, respectively. The disease control rate was 63.3%. The frequent AEs were proteinuria, hypertension, and hepatitis. Serious AEs included gastrointestinal bleeding, but none of the patients died from serious AEs. The discontinuation rate was 23.3%, and the median number of treatment cycles was 10.5 cycles. In total, 23.3% of the patients continued treatment after 1 year of therapy. The global health status/QoL and physical function scores showed less deterioration at baseline than at 3 and 6 months (median scores = 76.7, 71.6, and 64.1 in QoL and 84.7, 79.6, and 79.0 in physical function, respectively). The HCC18 symptom score index data showed a slow progression of symptom scores from baseline to 3 and 6 months (12.7, 19.6, and 22.3, respectively). CONCLUSION This study demonstrates that atezolizumab plus bevacizumab is effective and has a safety profile comparable with that of previous studies as first-line therapy for unresectable HCC in a real-world setting and in Thai populations. Data on PROs also demonstrate benefits in terms of patients' QoL and symptoms.