Comparing the clinical efficacy and safety of second-line targeted therapy and immunotherapy in patients with mid- to advanced stages of hepatocellular carcinoma - A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: The aim of this study was to examine the efficacy and safety of second-line immunotherapy and targeted treatment in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From January 2000 to January 2023, ProQuest, PubMed, Web of Science, Scopus, Embase, and the Cochrane Library databases were searched for randomized controlled trials (RCTs) using immunotherapy or targeted therapy as second-line therapy for mid-to-advanced stages of HCC. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) are all examples of measures of success. RESULTS: This analysis included twenty Randomized Clinical Trials (RCTs) from phases II and III. Collective data revealed better OS with immunotherapy (HR = 0.79; 95% CI: 0.67, 0.93 vs. 0.85; 95% CI: 0.78, 0.92), while the targeted therapy played a more effective role in PFS (0.67; 95% CI: 0.56, 0.81). Also, the second-line immunotherapy had a lower odds ratio of AEs of grades 3-5 than the targeted therapy did (OR = 1.75; 95% CI = 0.89, 3.46). CONCLUSIONS: Overall, it appears that targeted medication and immunotherapy as a second-line treatment strategy have generally improved substantially, as well as progression-free survival for patients with mid-to-advanced HCC. Although it is difficult to judge their efficiency, the occurrences of AEs were greater in targeted therapy compared to immunotherapy.

Effect of hyperphosphatemia on gene expression of the Na-Pi cotransporter in rats.

We investigated the effect of high phosphorus content on the sodium-phosphate cotransporter (NaPi-IIa and NaPi-IIl). Forty-eight Sprague-Dawley rats were divided into 3 groups: high-phosphorus group (HP) with fructose diphosphate sodium injection; self-manufactured low-phosphorus diet group (LP); and normal diet group (NP). At the 1st, 2nd, 4th, and 6th weeks, 4 rats from each group were sacrificed for detecting serum levels of calcium, phosphorus, and intact parathyroid hormone. Semi-quantitative retrovirus-polymerase chain reaction was used to detect the expression of NaPi-IIa and NaPi-III mRNA in kidney. At the 1st, 2nd, 4th, and 6th weeks, serum phosphorus and parathyroid hormone levels in HP group were significantly higher than those in LP and NP groups (P < 0.05). Serum calcium levels in the 3 groups showed no difference (P > 0.05). Comparing the expression of NaPi-IIa mRNA in HP group with LP and NP groups, NaPi-IIa mRNA expression was significantly reduced in HP group (P < 0.05), while NaPi-IIa mRNA expression in LP group began increasing at the 4th week (P < 0.05). At the 1st, 2nd, and 4th weeks, the expression of NaPi-III mRNA in HP, LP, and NP groups showed no clear differences (P > 0.05), while at the 6th week in HP group, NaPi-III mRNA expression was slightly increased compared to in LP and NP groups (P < 0.05). Hyperphosphatemia significantly affected NaPi-IIa and NaPi-III mRNA expression, and a factor promote an increase in intact parathyroid hormone independently of calcium.

Establishment and characterization of a rat model of hyperphosphatemia.

We established a rat model of hyperphosphatemia and investigated the systemic effects of high phosphorus (P). Sprague Dawley rats were randomly divided into high (HP), low (LP), and normal (NP) P groups (N = 12 each), which received injections of fructose diphosphate sodium, or were fed self-manufactured low phosphorus or normal diets, respectively. In each group, 4 rats were sacrificed at the first, third, and sixth week to detect the serum (Scr) and urinary creatinine and P, and calcium (Ca) levels. The HP group's serum P and intact parathyroid hormone (iPTH) were significantly higher than those in the other groups at the first, third, and sixth weeks, (P < 0.05); the LP group's serum P was lower than the NP group's at the third week (P < 0.05), while at the sixth week, the serum P and iPTH were lower (P < 0.05). No significant differences were detected for blood Ca+ (P > 0.05). The HP group's Scr increased (P < 0.01), whereas the fractional excretion decreased (P < 0.05) significantly. Thighbone and lumbar spine bone densities differed significantly between groups in the third week (P < 0.05); LP group densities were lower than NP group measures (P < 0.05). Crystallized stones were not observed microscopically following hematoxylin and eosin staining of the kidney. We successfully established a hyperphosphatemia rat model, and high blood P was found to significantly influence renal function and bone density. These results might provide a foundation to study the effects of hyperphosphatemia in rats.

Expression and clinical value of the soluble major histocompatibility complex class I-related chain A molecule in the serum of patients with renal tumors.

We investigated the expression and clinical value of the soluble major histocompatibility complex class I-related chain A (sMICA) molecule in the serum of patients with renal tumors. Sixty patients diagnosed with renal tumors were enrolled in the experimental group, whereas 20 healthy volunteers served as the control group. The sMICA levels were measured via enzyme-linked immunosorbent assay, and the results were analyzed in combination with data from pathol-ogy examination. The experimental group had a statistically significant higher sMICA level (P < 0.05) than the control group. The sMICA level was higher in patients with malignant tumors than in those with be-nign tumors. We also observed a positive relationship among different tumor-node-metastasis (TNM) pathological stages with more advanced diseases exhibiting higher sMICA levels. As a tumor-associated antigen, MICA has a close relationship with renal tumorigenesis and immune es-cape. Our results indicated that sMICA levels were related to tumor pathol-ogy, TNM stage, and metastasis. Therefore, sMICA might be a potential marker for tumor characteristics, prognosis, and recurrence prediction.

An efficacy trial of a mammalian cell-derived recombinant DNA hepatitis B vaccine in infants born to mothers positive for HBsAg, in Shanghai, China.

We conducted a randomized, double-blind clinical trial of an experimental mammalian cell-derived DNA hepatitis B vaccine (Betagen, Connaught Laboratories Ltd, Toronto, Canada) to determine its efficacy in infants born to mothers who were carriers of hepatitis B surface antigen (HBsAg). Four groups of 55 infants received injections as follows: (1) a licensed plasma-derived vaccine (Lanzhou, Lanzhou Institute for Biological Products, Lanzhou, People's Republic of China), 20 micrograms; (2) Betagen, 20 micrograms; (3) Betagen, 20 micrograms+hepatitis B immune globulin (HBIG); and (4) Betagen, 10 micrograms+HBIG. Vaccine injections were given at birth and at 1 and 6 months and HBIG was given at birth. The vaccines were compared to a historical placebo control group. The efficacy of Betagen alone was 82.6% compared to 51.0% for the Lanzhou. Efficacy of Betagen increased with the concomitant use of HBIG. No infants who were HBsAg negative at birth and/or were born to hepatitis B e antigen (HBeAg) negative mothers became carriers. The rate of HBsAg in infants receiving Betagen alone, and born to mothers who were HBeAg positive, decreased from 60% at birth to 20% by the ninth month, compared to 62.5% and 50% (respectively) for Lanzhou. The percentage of infants with protective levels of antiHBs was significantly higher for Betagen alone than for Lanzhou, but the geometric mean titre of antiHBs for responders was not significantly different. We have shown that Betagen alone is highly efficacious in preventing the development of hepatitis B in infants born to mothers who are carriers of HBsAg and is also highly effective in reducing the carriage of HBsAg in infants who are HBsAg positive at birth and/or born to HBeAg positive mothers.

PIP: Researchers assigned 220 infants born at 5 participating hospitals in Shanghai, China to receive either a 20mcg of an experimental recombinant DNA hepatitis B vaccine (Betagen), a licensed plasma derived hepatitis B vaccine (Lanzhou), 20 mcg of Betagen and hepatitis B immune globulin (HBIG), or 10mcg of Betagen and HBIG to determine the efficacy of Betagen in infants born to mothers with hepatitis B surface antigen (HBsAg) positive. Since China is a hyperendemic hepatitis B carrier area (in Shanghai, for example, prevalence rate is 57%), China hopes to reduce the carrier state via a low cost, safe, immunogenic, and efficacious recombinant vaccine. 20mcg of Betagen resulted in 82.6% efficacy which was significantly higher than that of Lanzhou (51%). The efficacy increased when HBIG was administered with the 20mcg of Betagen (92%). None of the infants born HBsAg negative and/or born to hepatitis B e antigen (HBeAg) mothers later became carriers. Further the HBsAg positive fell from 60-2-% in 9 months whereas these corresponding figures for those who received only Lanzhou were 62.5% and 50%. Even though the percentage of infants with protective levels of antiHBs stood much higher in those who received only Betagen than for those who received Lanzhou in all the months of follow up, except the 1st, their geometric mean titre of antiHBs was not statistically significant. Since Betagen prompted a quick antibody response which probably helped decrease HBsAg in the serum of those infants already positive for HBsAg at birth, it had an advantage over Lanzhou. In conclusion, Betagen given alone proved to be very efficacious in preventing hepatitis B in infants born to carriers of HBsAg. Further it was effective in reducing carriage of HBsAg in infants born HBsAg positive and/or born to HBeAg positive mothers.