New approach to anal cancer:Individualized therapy based on sentinel lymph node biopsy

Oncological treatment is currently directed toward a tailored therapy concept.Squamous cell carcinoma of the anal canal could be considered a suitable platform to test new therapeutic strategies to minimize treatment morbidity.Standard of care for patients with anal canal cancer consists of a combination of radiotherapy and chemotherapy.This treatment has led to a high rate of local control and a 60% cure rate with preservation of the anal sphincter,thus replacing surgical abdominoperineal resection.Lymph node metastases represent a critical independent prognostic factor for local recurrence and survival.Mesorectal and iliac lymph nodes are usually included in the radiation field,whereas the inclusion of inguinal regions still remains controversial because of the subsequent adverse side effects.Sentinel lymph node biopsies could clearly identify inguinal node-positive patients eligible for therapeutic groin irradiation.A sentinel lymph node navigation procedure is reported here to be a feasible and effective method for establishing the true inguinal node status in patients suffering from anal canal cancer.Based on the results of sentinel node biopsies,a selective approach could be proposed where node-positive patients could be selected for inguinal node irradiation while node-negative patients could take advantage of inguinal sparing irradiation,thus avoiding toxic side effects.

Alteration of the p53 gene during tree shrews' hepatocarcinogenesis

OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB_1; group B, only infected with HBV; group C, fed with AFB_1 alone; and group D normal control. The tree shrews underwent liver biopsy every. 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0±16.6 wk vs 153.3±5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (X^2≥5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology, compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB_1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB_1 may synergistically induce p53 gene mutation.

Inhibitory Effect of Angiogenesis Inhibitor TNP-470 on Human ACHN Renal Cell Carcinoma

The contribution of angiogenesis inhibitor TNP- 4 70 to the growth and m etastasis of ACHN renal cell carcinom a (RCC) was studied. TNP- 4 70 (40 m g/ kg,every two days) was ad- ministrated to BABL / c nude m ice bearing ACHN RCC. The mice were sacrificed after a treatment duration of 31days and the weight and volum e of subcutaneous tum ors as well as foci of lung m etastasis were m easured.The microvascular density(MVD) of the tumor as well as the PCNA index and apoptotic index of the tum or cells were evaluated imm unohistochem ically. Result showed that the growth of ACHN RCC was suppressed significantly and none metastasis was ob- served in TNP- 4 70 - treated m ice. Compared with the control group,the MVD was decreased m arkedly (P<0 .0 1) and the apoptotic index was increased significantly (P<0 .0 1) in the treated group. The tumor volume was positively correlated to the MVD (r=0 .714 4 ,P<0 .0 1) and in- versely correlated to the apoptotic index(r=- 0 .86 0 7,P<0 .0 1) ,and MVD was conversely cor- related to the apoptotic index.It was determ ined that TNP- 4 70 could effectively inhibit angiogene- sis of ACHN RCC,which resulting in ischemia and hypoxia,leading to increased apoptosis,thus obviously suppressing the growth and metastasis of ACHN RCC in nude m ice.