Family history of cancer in Chinese gastric cancer patients

Objective:The aim of the study was to investigate the influence of gastric cancer family history in the gastric cancer (GC) patients. Methods: Gastric cancer family histories within second degree relatives and clinicopathological features were obtained for 497 patients. Results:Of the 497 probands,235 probands were incorporated into familial gastric cancer (FGC) group (there were at least two GC members in the family); 262 probands were included in the non-FGC group (relatives only affected with non-GCs). Of 614 tumors in relatives,GC was the most frequent,followed by lung cancer,esophageal cancer,hepatocellular cancer,colorectal cancer,urogenital cancer,breast cancer,and pancreatic cancer. Most affected members aggregated within first-degree relatives. The ratio of males to females in affected first-degree relatives was usually higher in male probands. Paternal history of GC was a strong risk for GC in males,while risk of GC by maternal history of GCs was increased in females. Difference in tumor histological types between the two groups was derived from an excess of diffuse GC in non-FGC male probands. The lower site was the most frequent tumor location in all subgroups. Conclusion:Distribution of associated non-GCs in a family history of GC may vary with geographic areas. GC may have different genetic and/or environmental etiology in different families,and a certain subtype may be inherited in a male-influenced fashion.

KCNJ15 deficiency promotes drug resistance via affecting the function of lysosomes

The altered lysosomal function can induce drug redistribution which leads to drug resistance and poor prognosis for cancer patients.V-ATPase,an ATP-driven proton pump positioned at lysosomal surfaces,is responsible for maintaining the stability of lysosome.Herein,we reported that the potassium voltage-gated channel subfamily J member 15(KCNJ15)protein,which may bind to V-ATPase,can regulate the function of lysosome.The deficiency of KCNJ15 protein in breast cancer cells led to drug aggregation as well as reduction of drug efficacy.The application of the V-ATPase inhibitor could inhibit the binding between KCNJ15 and V-ATPase,contributing to the amelioration of drug resistance.Clinical data analysis revealed that KCNJ15 deficiency was associated with higher histological grading,advanced stages,more metastases of lymph nodes,and shorter disease free survival of patients with breast cancer.KCNJ15 expression level is positively correlated with a high response rate after receiving neoadjuvant chemotherapy.Moreover,we revealed that the small molecule drug CMA/BAF can reverse drug resistance by disrupting the interaction between KCNJ15 and lysosomes.In conclusion,KCNJ15 could be identified as an underlying indicator for drug resistance and survival of breast cancer,which might guide the choice of therapeutic strategies.

Clinical Implications of HER-2 and P53 in Taxane-Based and Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer

OBJECTIVE To evaluate the predictive value of humanepidermal growth factor receptor-2 (HER-2) and P53 in taxane-based and anthracycline-based neoadjuvant chemotherapy (NAC)in breast cancer.METHODSSixty-two patients with breast cancer wereincluded in this study.Twenty-two patients were treated withtaxane-based (taxane group) and 40 with anthracycline-based(anthracycline group).ER,PR,c-erbB2 and P53 were detected byimmunohistochemistry staining before NAC,and FluorescenceIn Situ Hybridization(FISH) was used to detect the HER-2 geneamplification for the cases with the expression of c-erbB2 proteinas (++) or (+++).The efficacy of the regimens was evaluated afterNAC.RESULTS In the anthracycline group,objective response (OR)was observed in 30 out of 40 patients (75%),whereas no response(NR) was observed in 10 patients (25%).In the taxane group,ORwas observed in 15 patients out of 22 patients (68.2%),whereasNR was observed in 7 patients (31.8%).HER-2-negative status wascorrelated with a high OR in both taxane-based and anthracycline-based NAC (P = 0.023 and P = 0.029),whereas P53-negative statuswas correlated with high OR rate in anthracycline-based NAC (P= 0.041).The significant difference of the CR rates was observedbetween the patients took<4 cycles and>4 cycles NAC (4.65% vs.21.05%,P<0.05).CONCLUSION The patients with HER-2 gene non-amplicationmay be sensitive to both taxane-based and anthracycline-basedchemotherapy;the patients without P53 overexpression maysuitable to select anthracycline-based chemotherapy;and properincreased NAC cycles may increase CR rates.

Distribution pattern of solitary lymph node in middle third gastric cancer

Objective: To investigate the distribution pathway of sentinel lymph nodes (SLN) in middle third gastric carci-noma, as the foundation for rational lymphadenectomy. Methods: 52 cases of middle third tumors with solitary lymph nodes from 1852 gastric carcinomas were selected. The locations and histological types of metastatic lymph nodes were analyzed retrospectively. Results: Of 52 solitary node metastases cases, 37 were limited to perigastric nodes (N1), while 15 with skipping metastasis. In the 35 cases with tumor of lesser curvature, there were 17 cases found lymph nodes of the lesser curvature side (No. 3), 5 cases involved lymph nodes of the greater curvature (No. 4), and 8 cases with lymph nodes of the left gastric artery (No. 7). In the 17 cases with tumor of greater curvature, 7 cases spread to No. 4, while 3 metastasized to lymph nodes of the spleen hilum (No. 10). The difference of the histological types in groups N1 and over N1, were not statistically significant (P > 0.05). Conclusion: Adjacent metastasis formed the primary distribution pattern of SLN in middle third gastric carcinoma, transversal and skipping metastases being also notable.

Relationship between FHIT Expression and HPV Status in Vulvar Squamous Cell Carcinomas

OBJECTIVE To investigate the relationship between fragilehistidine triad (FHIT) depletion and human papillomavirus (HPV)status in the vulvar squamous cell carcinomas (VSCC).METHODS Immunohistochemical method was used to detectthe expression of FHIT protein in 42 cases of VSCC and 10 casesof normal vulvar tissues. PCR was used to detect HPV infectionstatus. We analyzed the relationship of the expression of FHITprotein between the 2 groups: HPV positive and HPV negative, aswell as the clinically pathological characteristics.RESULTS The expression of FHIT was positive in all normal vul-var tissues, and 71.4% was depletion in VSCC (P < 0.01). Abnormalexpression of FHIT was significantly correlated with pathologicalgrade (P < 0.05). There was a significant difference between FHITdepletion and HPV infection based on the statistial analysis (P <0.05).CONCLUSION The FHIT depletion is related to occurrenceand development of VSCC, and the abnormal expression of FHITsignificantly correlates with HPV infection.

FSIP1 enhances the therapeutic sensitivity to CDK4/6 inhibitors in triple-negative breast cancer patients by activating the Nanog pathway

CDK4/6 inhibitors are routinely recommended agents for the treatment of advanced HR+HER2-breast cancer.However,their therapeutic effectiveness in triple-negative breast cancer(TNBC)remains controversial.Here,we observed that the expression level of fibrous sheath interacting protein 1(FSIP1)could predict the treatment response of TNBC to CDK4/6 inhibitors.High FSIP1 expression level was related to a poor prognosis in TNBC,which was associated with the ability of FSIP1 to promote tumor cell proliferation.FSIP1 downregulation led to slowed tumor growth and reduced lung metastasis in TNBC.FSIP1knockout caused cell cycle arrest at the G0/G1 phase and reduced treatment sensitivity to CDK4/6 inhibitors by inactivating the Nanog/CCND1/CDK4/6 pathway.FSIP1 could form a complex with Nanog,protecting it from ubiquitination and degradation,which may facilitate the rapid cell cycle transition from G0/G1 to S phase and exhibit enhanced sensitivity to CDK4/6 inhibitors.Our findings suggest that TNBC patients with high FSIP1 expression levels may be suitable candidates for CDK4/6 inhibitor treatment.