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Vascular endothelial growth factors (VEGFs) consist of five molecules (VEGFA through D as well as placental growth factor) which are crucial for regulating key cellular and tissue functions. The role of VEGF and its intracellular signaling and downstream molecular pathways have been thoroughly studied. Activation of VEGF signal transduction can be initiated by the molecules' binding to two classes of transmembrane receptors: (1) the VEGF tyrosine kinase receptors (VEGF receptors 1 through 3) and (2) the neuropilins (NRP1 and 2). The involvement of Rho GTPases in modulating VEGFA signaling in both cancer cells and endothelial cells has also been well established. Additionally, different isoforms of Rho GTPases, namely, RhoA, RhoC, and RhoG, have been shown to regulate VEGF expression as well as blood vessel formation. This review article will explore how Rho GTPases modulate VEGF signaling and the consequences of such interaction on cancer progression., Competing Interests: The authors declare that they have no conflict of Interest., (Copyright © 2020 Nada El Baba et al.)

Prediction of the timing of platelet recovery after chemotherapy and hematopoietic stem cell transplantation (HSCT) allows for optimal platelet transfusion. We assessed the clinical utility of the percentage value of the immature platelet fraction (IPF%) monitored using an XE-2100 automated hematology analyzer to predict the timing of platelet recovery after chemotherapy and HSCT. The IPF% was serially monitored in 31 patients with cancer who received 66 courses of chemotherapy and HSCT. In patients with cancer undergoing chemotherapy and HSCT, a transient increase in IPF% was observed 1-11 days prior to platelet recovery (>30 × 10⁹ /l). In patients undergoing chemotherapy with a peak IPF% >10%, platelet recovery occurred significantly earlier than in those with IPF% peak values ≤10% (median periods were 2 and 5 days; P < 0.05). Platelet recovery appears to occur earlier in patients undergoing HSCT with a peak IPF% >10% than in those with IPF% peak values ≤10% (median periods were 2 and 6 days). Thus, the IPF% peak value is a useful parameter for predicting the timing of platelet recovery after chemotherapy and HSCT and has the potential to facilitate optimal platelet transfusion., (© 2010 Blackwell Publishing Ltd.)

For 12 patients with terminal stage cancer who died within the period from June 1995 to the present, we retrospectively evaluated the correlation between the "information" concerning disclosure of the "diagnosis," "pathology," and "prognosis," with the length of the last admission before the death, "sedation" near death, and the choice of "do not resuscitate (DNR)." The average length of admission before death was markedly shorter for patients who had been told either the "diagnosis," "pathology," or "prognosis" than for patients who had not. A statistically significant difference was observed between those who had been told and those who had not been told the "pathology." Similarly, "sedation" tended to be done for those who had been provided with information on cancer. It was suggested that telling patients with terminal stage cancer the truth about "diagnosis," "pathology," and "prognosis" is important for them to spend a fulfilling terminal stage.

Clinical efficacy of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT) in combination with plasma exchange and interleukin (IL-2) was investigated in 24 patients with advanced cancer. Partial response (PR) was found in 4 patients (20%), including 1 primary liver tumor, 1 metastatic lung tumor from renal cancer and 2 malignant pleural effusions from gastric and lung cancer. Based on these results new AIT in combination with plasma exchange, OK-432, IL-2 and cyclophosphamide was designed to target liver and lung tumors, in which LAK cells and other drugs were administered through the catheter located in the feeding artery of the tumor. Out of ten patients treated, 1 (10%) with metastatic liver tumor from gallbladder cancer was evaluated as PR. It is suggested that a strategy to enhance tumor accumulation and recognition of LAK cells should be attempted for development of gastrointestinal cancer therapy with AIT.

The clinical efficacy of intratumoral (IT) OK-432 immunotherapy in advanced cancer patients was investigated. Furthermore, the infiltration of lymphocyte subsets into the tumor tissues after the IT administration of OK-432 was also immunohistologically examined in order to analyze the mechanism of action of OK-432 immunotherapy. Forty-four patients with advanced cancer were treated with IT OK-432 immunotherapy. Ten KE (1 mg) of OK-432 was given either daily or on every second day and repeated as often as possible, the mean frequency of OK-432 injections being 18.1 +/- 14.5 times, ranging between 5 and 25 administrations. Thirty-one of the 44 patients were evaluable, 3 of whom (9.7 per cent) developed a partial response and 5 (16.1 per cent) a minor response. Intratumoral OK-432 immunotherapy, however, did not necessarily prolong the survival time. Leu 1, 3 and 7 reactive cells infiltrated into the tumor tissues treated by OK-432 injection, more frequently, when compared with cells which had been treated by recombinant TNF injection. Thus, it was suggested that IT OK-432 immunotherapy might be effective for the local control of tumor growth through the host mediated action, and that, in combination with systemic therapy, may enhance the clinical effects and prolong the survival time in advanced cancer patients.

The immunosuppression caused by surgical stress in cancer therapy may affect the prognosis of patients by enhancing the residual tumors. An investigation of changes of lymphocyte subsets and suppressor cell activity during the postoperative course was performed for the analysis of the immunosuppression caused by the surgical stress in patients with gastrointestinal cancer. In patients undergoing the surgical stress of total gastrectomy or esophageal resection, CD4+2H4- (helper T) and CD8+CD11-(cytotoxic T) cells significantly depressed on day 1 after operation and remained until day 7. In these patients, CD4+2H4+ (suppressor inducer T) cells significantly increased from just after the operation, remained to increase until day 1 after operation and recovered to the preoperative level thereafter. Concanavalin A-induced suppressor cell activity peaked on day 4 and decreased thereafter. However, in patients with benign disease, decreases of helper and cytotoxic T cells were found to a slight degree. The population of lymphocytes with surface receptors for a soluble suppressor factor significantly increased on day 1 after operation in patients receiving esophageal resection and continued to increase until day 30. In patients with preoperative treatment of PSK and cyclophosphamide, the decreases in helper and cytotoxic T cells and the increase in suppressor inducer T cells were significantly blocked during the postoperative course. Thus, these results indicate that extensive surgical stress such as total gastrectomy and esophageal resection may be attributable to the immunosuppression produced by the induction of suppressor cells, and the necessity of pre- and post- operative immunotherapies may be indicated for a better prognosis.

The clinical efficacy of intratumoral (IT) administration of BRM in 157 patients with unresectable or recurrent tumors was investigated, and the infiltration of lymphocyte subsets into tumor tissues after IT administration of BRM was immunohistologically examined, to analyse its action mechanism. BRMs used in this study were OK-432, tumor necrosing factor (TNF), whole peptide glucagon (WPG), interferon (IFN)-alpha, IFN-beta, IFN-gamma and interleukin-2 (IL-2). Among them, one hundred thirty-one patients were evaluable for clinical effects, and the therapeutic response rate (CR + PR) was determined in 11/131 (8.4%). Higher therapeutic responses were found in the patients with esophageal cancer, pancreatic cancer and breast cancer, respectively. As for the relationship between the clinical efficacy of IT administration of BRM and the injected sites, the injection into metastatic lesions was more effective than that into the primary or local recurrence. A increase of lymphocyte infiltration after IT BRM immunotherapy and a variety of lymphocyte subsets in tumor tissue injected with any BRMs were found immunohistologically. These results suggest that IT BRM immunotherapy may be effective for the control of tumor growth locally through host-mediated action.

Background Controversy exists regarding the optimal margin of surgical excision for cutaneous squamous cell carcinoma (cSCC). Japanese clinical practice guidelines for skin cancer (second edition) recommend an excision with a 4–6-mm clinical margin for low-risk cSCC and >6-mm clinical margin for high-risk cSCC. However, it is difficult to follow this guideline for all cSCCs because high-risk cSCCs frequently occur on the face or in older patients. The purpose of this study was to investigate the correlation between surgical margin and prognosis in patients with cSCC. Methods Patients with cSCC who underwent surgical excision of the primary site between 2011 and 2019 at Saitama Medical University International Medical Center were included in this retrospective observational study. Patients were divided into two groups: group A (standard surgery with guideline-recommended margin) and group B (modified surgery with narrow margin). Overall survival (OS), relapse-free survival (RFS), local recurrence-free survival (LRFS), regional metastasis-free survival (RMFS), and distant metastasis-free survival (DMFS) were compared between the two groups. Results A total of 107 patients with cSCC were included in this study: 39 in group A and 68 in group B. There were no significant differences in patient characteristics such as sex, tumor border, and risk factors; age and tumor size differed between groups. There were no statistically significant differences in OS (p=.470), LRFS (p=.631), RMFS (p=.502), and DMFS (p=.475) between the two groups. However, RFS was significantly lower in group A than in group B (p=.049). Conclusions This study did not reveal a significant impact of clinical margin on OS in patients with cSCC. Although this conclusion may have been limited by selection bias, excision with narrower margins than those suggested by current guidelines may be appropriate. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]