Development of the Relationship between Angiogenesis and Tumor Dormancy

Tumor dormancy, a complex and still poorly understood phenomenon, has been defined by the long-term persistence of occult can- cer cells during tumor progression. Recurrence and metastasis may occur just because of an activation of a small portion of the tumor cells. In our view, sustained angiogenesis is considered essential in triggering invasive tumor growth. Here we analyze the correlation between angiogenesis and tumor dormancy, the establishment of tumor dormancy models, the imaging strategies and the new biomarkers for dececting microscopic tumors before or during the angiogenic switch. It imperative to understand the role of an- giogenesis in tumor dormancy, as this will accelerate the development of anti-angiogenesis techniques to induce dormancy and/or eradicate dormant disease.

The Efficacy of a Formula Food for Preventing Postoperative Recurrence in a Tumor Dormancy Model

Objective To establish a lung cancer dormancy mouse model and verify the effects of Wushen(WS),a formula food,on postoperative recurrence.Methods We established a Lewis cell tumor dormancy model system that definitively links surgery and the subsequent wound-healing response to the outgrowth of lung cancer cells.We used this model to observe the effects of WS on the postoperative recurrence and the nutritional status of the mice.Finally,the immunocyte subtypes and cytokine levels in the serum and spleens of mice were detected by flow cytometry and ELISA.Results The recurrence rate in the WS group was obviously lower than that in the control group.Wushen increased the body weights and serum albumin levels of the mice.The levels of NK,Gr1+CD11b+CD3+CD8+and CD3+CD4+T cells in the spleens of mice in the WS group were also increased.Compared with the control group,the levels of CD4+IFN-γ+,CD4+IL-2 and CD4+/IL-10+in the spleens of mice in the WS group were decreased.Wushen also seemed to decrease the levels of IL-6 and TNF-α,but the decrease was not significant.Conclusion The postoperative lung cancer recurrence model was successfully established.Wushen inhibited postoperative recurrence,apparently by regulating the level of immune cell subtypes and cytokines in the serum and spleen.

Chemotherapy with enteric-coated tegafur/uracil for advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, including Japan. Although the development of imaging modalities has made the early diagnosis of HCC possible, surgically resectable cases are relatively uncommon because of hepatic function reserve and/or an advanced stage at presentation. Several modalities, such as transcatheter arterial chemoembolization, percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation are reportedly useful in treating patients with non-resectable disease. However, unfortunately, many HCC patients have tumor recurrence. The overall prognosis of patients with HCC is very poor, and treatment of the advanced form is still problematic. In this article, we review the clinical efficacy and toxicity of enteric-coated tegafur/uracil in the treatment of patients with advanced non-resectable HCC.

Late onset pulmonary metastasis more than 10 years after primary sigmoid carcinoma

According to current guidelines, follow-up of patients with colorectal cancer is ended after five years. Also, chest X-ray is not part of standard investigation during follow-up. We describe a case of a 74-year-old patient, more than ten years after a sigmoid resection because of carcinoma of the sigmoid. No recurrence was detected during intensive follow-up. However, ten years after resection of the sigmoid adenocarcinoma, complaints of coughing induced further examination with as result the detection of a solitary metastasis in the left lung of the patient. Within half-a-year after metastasectomy of the lung metastasis, she presented herself with thoracic pain and dyspnea resulting in discovering diffuse metastasis on pulmonary, pleural, costal and muscular level. Five year follow-up of colorectal carcinoma without chest X-ray can be questioned to be efficient. The growing knowledge of tumor biology might in future adjust the duration and frequency of diagnostic follow-up to prevent(late) recurrence in patients with colorectal carcinoma.

Ovarian growing teratoma syndrome with multiple metastases in the abdominal cavity and liver:A case report

BACKGROUND Growing teratoma syndrome(GTS)is an unusual presentation of an amazing transformation of teratoma from malignant to benign on pathology during or after systemic or intraperitoneal chemotherapy.The definitive pathogenesis is still not fully understood due to the lack of large-sample studies.CASE SUMMARY A 53-year-old woman underwent radical surgery and postoperative intraperitoneal chemotherapy due to immature teratoma of the right ovary at the age of 28.She remained well during a 25-year follow-up period after surgery.Multiple asymptomatic solid masses were found in the liver on ultrasonography a month ago.Enhanced computed tomography(CT)of the abdomen revealed multiple masses in the abdominal cavity.The largest one was located in the posterior peritoneum next to the sixth segment of the right liver,about 7.9 cm×7.5 cm in size.Three masses were present inside the liver,and one mass was in the right pelvic floor.Multiple lumps in the abdominal cavity were completely removed by surgery.During the operation,multiple space-occupying lesions were seen,ranging in size from 0.5 to 3 cm,and grayish white in color and hard in texture.Ovarian GTS was finally diagnosed based on postoperative pathology.After surgery,she recovered uneventfully.During a 3-year follow-up,the patient remained free of the disease without any recurrence on CT scan.CONCLUSION GTS is a rare phenomenon characterized by conversion of immature teratoma to mature one during or after chemotherapy and presents as growing and metastasizing masses.The pathogenesis of GTS is unclear,and the prognosis is good after surgical resection.

Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer treatment.Since tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the tumor.Based on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against therapy.We discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"popula-tions.Furthermore,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer cells.Beyond understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to treatment.More-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in tumors.Overall,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

Priming cancer cells for drug resistance： role of the fibroblast niche

Conventional and targeted chemotherapies remain integral strategies to treat solid tumors. Despite the large number of anti-cancer drugs available, chemotherapy does not completely eradicate disease. Disease recurrence and the growth of drug resistant tumors remain significant problems in anti-cancer treatment. To develop more effective treatment strategies, it is important to understand the underlying cellular and molecular mechanisms of drug resistance. It is generally accepted that cancer cells do not function alone, but evolve through interactions with the surrounding tumor microenvironment. As key cellular components of the tumor microenvironment, fibroblasts regulate the growth and progression of many solid tumors. Emerging studies demonstrate that fibroblasts secrete a multitude of factors that enable cancer cells to become drug resistant. This review will explore how fibroblast secretion of soluble factors act on cancer cells to enhance cancer cell survival and cancer stem cell renewal, contributing to the development of drug resistant cancer.