KITENIN (KAI1 C-terminal interacting tetraspanin) promotes invasion and metastasis in mouse colon cancer models. In the present study, we evaluated the effects of KITENIN knockdown by intravenous administration of short hairpin RNAs (shRNAs) in an orthotopic mouse colon cancer model, simulating a primary or adjuvant treatment setting. We established orthotopic models for colon cancer using BALB/c mice and firefly luciferase-expressing CT-26 (CT26/Fluc) cells. Tumor progression and response to therapy were monitored by bioluminescence imaging (BLI). In the primary therapy model, treatment with KITENIN shRNA substantially delayed tumor growth (P = 0.028) and reduced the incidence of hepatic metastasis (P = 0.046). In the adjuvant therapy model, KITENIN shRNA significantly reduced the extent of tumor recurrence (P = 0.044). Mice treated with KITENIN shRNA showed a better survival tendency than the control mice (P = 0.074). Our results suggest that shRNA targeting KITENIN has the potential to be an effective tool for the treatment of colon cancer in both adjuvant and metastatic setting.
Animals ; Carrier Proteins/*genetics/metabolism ; Cell Line, Tumor ; Colonic Neoplasms/genetics/mortality/pathology/*therapy ; Disease Progression ; Liver Neoplasms/prevention & control/*secondary ; Membrane Proteins/*genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis/*prevention & control ; Neoplasm Recurrence, Local/genetics/*prevention & control ; RNA Interference ; RNA, Small Interfering/*therapeutic use ; Tumor Markers, Biological/genetics

The death of patients with gastric cancer is mainly due to its recurrence and metastasis, and circulating tumor cell (CTC) is the necessary condition of metastasis. As liquid biopsy, CTC detection has its certain clinical significance. The detection is required after enrichment because circulating tumor cells are rare. Many enrichment methods have been developed: methods based on physical characteristics of TCT, like density, size and dielectric properties and so on; immunogenicity, like Cell Search System; and microfluidic chip technology. The immunofluorescence is commonly used to identify CTC in gastric cancer and the isolated CTC can also be used for the following analysis on the level of nucleic acid, protein and gene regulation. Detection of CTC in gastric cancer is helpful to judge the prognosis, assess staging, monitor the curative effect and guide the development of drug. There are many challenges for clinical transformation of CTC: the lower enrichment efficiency, the less specific surface markers, the uncertain diagnostic efficiency and so on, but it also has the good research prospect because it is non-invasive, repeatable and can real-time monitor the condition and guide the clinical treatment compared with pathological biopsy. In this paper, the detection and identification methods, and clinical value of CTC in gastric cancer patients are reviewed.
Biomarkers, Tumor ; Biopsy ; Cell Separation ; methods ; Cytodiagnosis ; methods ; Flow Cytometry ; methods ; Fluorescent Antibody Technique ; methods ; Humans ; Microchip Analytical Procedures ; methods ; Neoplasm Recurrence, Local ; prevention & control ; Neoplasm Staging ; methods ; Neoplastic Cells, Circulating ; metabolism ; pathology ; Prognosis ; Secondary Prevention ; Stomach Neoplasms ; blood ; diagnosis ; genetics ; therapy ; Treatment Outcome

INTRODUCTIONOur study investigates whether an approximation of breast cancer molecular subtypes using the hormone receptors and HER-2 status prognosticates for disease control after breast conservation therapy (BCT) in node-negative Asian breast cancer patients.

METHODS AND MATERIALSWe retrospectively reviewed 541 women with node-negative breast cancers treated with BCT between 1989 and 2007. Hormone receptors and HER-2 status were obtained from patients' histological report. All patients received radiotherapy. Thirty-six percent and 68% of women received chemotherapy and hormonal treatment respectively.

RESULTSMedian follow-up of patients is 72 months. Five-year local recurrence free survival (LRFS) is 97.2% for the cohort but differs between subtypes: luminal A, 0.8%; luminal B, 1.4%; HER-2, 3.6% and basal-like, 12.7% (P = 0.047). The 5-year distant disease free survival (DDFS) is 96.4% for the cohort but differs between subtypes: luminal A, 98.2%; luminal B, 92.6%; HER-2, 89.5% and basal-like, 91.5% (P = 0.019). The 5-year disease free survival (DFS) is 94.4% for the cohort but differs between subtypes: luminal A, 97.4%; luminal B, 92.7%; HER-2, 86.3% and basal-like, 85.0% (P = 0.007). Univariate analysis with luminal A as baseline revealed an association of the other 3 subtypes with decreased DFS (P = 0.007), Hazard Ratio (HR) of 2.2, 4.4 and 3.3 to Luminal B, HER-2 and basal subtypes, respectively. On multivariate analysis, HER-2 subtype (AHR = 3.3, 95% CI, 1.1 to 9.8, P = 0.036) and basal-like subtype (HR = 3.5, 95% CI, 1.2 to 9.9, P = 0.019) prognosticate adversely for DFS.

CONCLUSIONThe combination of hormone receptors and HER-2 status can be used as surrogates for molecular subtypes in Asian breast cancer patients with node-negative disease to prognosticate LRFS, DFS and DDFS.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; genetics ; pathology ; prevention & control ; Female ; Humans ; Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Prognosis ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; genetics ; Receptors, Estrogen ; genetics ; Receptors, Progesterone ; genetics ; Retrospective Studies ; Risk Assessment ; Survival Analysis ; Treatment Outcome

In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.
Biomedical Research/*trends ; Breast Neoplasms/therapy ; Combined Modality Therapy ; Dioxoles ; Endometrial Neoplasms/therapy ; Female ; Genital Neoplasms, Female/genetics/*therapy ; Humans ; Immunotherapy ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Ovarian Neoplasms/prevention & control/therapy ; Papillomavirus Vaccines ; Precision Medicine ; Tetrahydroisoquinolines ; Uterine Cervical Neoplasms/prevention & control/therapy/virology ; Uterine Neoplasms/therapy

OBJECTIVETo observe the effect of postoperative anti-viral therapy using lamivudine and thymosin alpha1 on recurrence of hepatocellular carcinoma (HCC) coexisting with active hepatitis B.

METHODSFrom Jan. 2000 to Dec. 2002, 33 HCC patients with coexisting with active hepatitis B were randomized into two groups: Group I (n = 17) received hepatectomy only, and Group II (n = 16) received hepatectomy and postoperative therapy using lamivudine plus thymosin alpha1. The suppression of HBV-DNA, HBeAg seroconversion rate, tumor recurrence rate and median survival in the two groups were observed and compared.

RESULTSIn Group II and Group I, the 1-year HBV-DNA suppression rate was 100.0% vs 6.0% (P < 0.01), HBeAg seroconversion rate was 62.5% vs 5.9% (P < 0.05), tumor recurrence rate was 81.3% vs 95.5% (P > 0.05), the recurrence time was 7.0 vs 5.0 months (P < 0.01) and median survival 10.0 vs 7.0 months (P < 0.01).

CONCLUSIONAnti-viral therapy using lamivudine and thymosin alpha1 postoperatively may suppress the HBV reaction, delay the recurrence and prolong the survival for patients with HCC with coexisting active hepatitis B.

Adult ; Aged ; Carcinoma, Hepatocellular ; surgery ; therapy ; virology ; DNA, Viral ; drug effects ; Female ; Hepatectomy ; methods ; Hepatitis B ; genetics ; therapy ; Humans ; Lamivudine ; therapeutic use ; Liver Neoplasms ; surgery ; therapy ; virology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Period ; Reverse Transcriptase Inhibitors ; therapeutic use ; Survival Rate ; Thymosin ; analogs & derivatives ; therapeutic use