Clinical Analysis of Autologous Peripheral Blood Hematopoietic Stem Cells Mobilization and Collection in Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the factors influencing collection of autologous peripheral blood hematopoietic stem cells in lymphoma patients.@*METHODS@#Clinical data of 74 patients who received autologous peripheral blood hematopoietic stem cells mobilization and collection in the 940th Hospital of Joint Logistic Support Force of PLA from April 2009 to April 2021 were collected. The effects of gender, age, disease type, stage, course of disease, chemotherapy cycle number, relapse, radiotherapy, disease status and blood routine indexes on the day of collection on peripheral blood hematopoietic stem cell collection were analyzed.@*RESULTS@#The success rate of collection was 95.9%(71/74), and the excellent rate of collection was 71.6%(53/74). There was a significantly statistical differentce in the number of CD34+ cells in grafts collected from patients with chemotherapy cycle ≤6 and >6 ［(9.1±5.2)×106/kg vs (6.4±3.7)×106/kg, P=0.031］. The number of CD34+ cells in the first collection was positively correlated with WBC count, hemoglobin, platelet count, neutrophil count, lymphocyte count, monocyte count and hematocrit value on the day of collection ( r value was 0.424,0.486,0.306,0.289,0.353,0.428,0.528, respectively). WBC count, hemoglobin, monocyte count and hematocrit value have higher predictive value for the first collection of CD34+ cells. The area under the receiver operating characteristic was 0.7061,0.7845,0.7319,0.7848, respectively.@*CONCLUSION@#Low dose CTX and VP16 chemotherapy combined with G-CSF can effectively mobilize autologous peripheral blood stem cells. The cycle number of chemotherapy relates to the collection of autologous peripheral blood stem cells. After mobilization, the success of the first collection can be better predicted by the blood routine indexes.

Oral metronomic chemotherapy for recurrent & refractory epithelial ovarian cancer: A retrospective analysis

Background & objectives: Advanced epithelial ovarian cancer (EOC) is associated with dismal outcome and progression-free survival (PFS) shortens with each subsequent relapse. For patients with recurrent and platinum refractory disease, therapeutic options are limited. Oral metronomic therapy (OMT) is associated with symptomatic relief and stable response in a significant proportion of patients. We retrospectively evaluated the outcome of patients with EOC treated with OMT at a tertiary care hospital in north India. Methods: Between January 2011 to December 2017, 36 EOC patients received OMT. Patients' median age was 50 yr (range, 38-81 yr) and they had received a median of two lines of prior chemotherapy. OMT regimen included a combination of cyclophosphamide, etoposide (VP-16) and celecoxib with or without pazopanib along with supportive care. Response rates and outcomes were ascertained using the Gynecological Cancer Intergroup Guidelines. The toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03. Results: The median CA-125 before initiating OMT was 160 U/ml (range, 42.23-5330 U/ml). The median interval between last chemotherapy and starting OMT regimen was 159 days (range, 1-1211 days). The overall response rate was 50 per cent. The median progression-free survival (PFS) was 8.2 months [95% confidence interval (CI): 5.03-10.33], and the median overall survival was 38 months (95% CI: 25.6-NR). Patients who received two lines of chemotherapy before OMT (P=0.052) and those who received pazopanib-based OMT (P=0.0513) had better PFS. Interpretation & conclusions: For patients with relapse and refractory EOC, OMT could be a reasonable option. A combination of oral etoposide (VP-16) and pazopanib needs further evaluation in a large number of patients in a randomized trial.

Protection effect of hepatocyte growth factor on tumor cells from apoptosis and its mechanism / 中国药学杂志

OBJECTIVE: To investigate the protection of hepatocyte growth factor (HGF) on 5 kinds of tumor cells (B cell lymphoma cell line Raji, human acute myeloid leukemia cell line HL-60, cervical cancer cell line HeLa, prostate cancer cell line PC-3, and non-small cell lung cancer cell line A549) from apoptosis induced by etoposide (VP-16). METHODS: Normal control group, drug group, and HGF protection group were set. CCK-8 assay was used to measure proliferation inhibition on 5 kinds of tumor cells by VP-16. Quantitative and qualitative analysis on 5 kinds of tumor cells was performed through acridine orange (AO) fluorescent staining, flow cytometry, HE staining, and transmission electron microscopy. RESULTS: CCK-8 assay revealed that the concentrations of VP-16, which can significantly inhibit the proliferation of Raji, HL-60, PC-3, HeLa, and A549 cell lines, were 100, 1,400, 200, and 200 μg·mL-1, respectively. The typical morphologic changes of cell apoptosis were observed under transmission electronic microscope. Flow cytometry showed that the apoptotic rates of tumor cells in the drug groups were significantly higher than those in normal control group (P>0.01, P>0.05) and in HGF protection groups (P>0.01, P>0.05). AO and HE staining revealed that cells in normal control group appeared to have regular cell morphology, but the cells apoptotic rates in the drug groups were significantly higher than those in normal control groups (P>0.01, P>0.05) and in HGF protection groups (P>0.01, P>0.05). CONCLUSION: HGF can significantly protect 5 kinds of tumor cells from apoptosis induced by VP-16. The mechanism need further investigation.

Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells

BACKGROUND: A limitation in the number of insulin-producing pancreatic beta-cells is a special feature of diabetes. The identification of alternative sources for the induction of insulin-producing surrogate beta-cells is a matter of profound importance. PDX-1/VP16, BETA2/NeuroD, and MafA overexpression have been shown to influence the differentiation and proliferation of pancreatic stem cells. However, few studies have been conducted using adult animal pancreatic stem cells. METHODS: Adult pig pancreatic cells were prepared from the non-endocrine fraction of adult pig pancreata. Porcine neonatal pancreas cell clusters (NPCCs) were prepared from neonatal pigs aged 1-2 days. The dispersed pancreatic cells were infected with PDX-1/VP16, BETA2/NeuroD, and MafA adenoviruses. After infection, these cells were transplanted under the kidney capsules of normoglycemic nude mice. RESULTS: The adenovirus-mediated overexpression of PDX-1, BETA2/NeuroD and MafA induced insulin gene expression in NPCCs, but not in adult pig pancreatic cells. Immunocytochemistry revealed that the number of insulin-positive cells in NPCCs and adult pig pancreatic cells was approximately 2.6- and 1.1-fold greater than those in the green fluorescent protein control group, respectively. At four weeks after transplantation, the relative volume of insulin-positive cells in the grafts increased in the NPCCs, but not in the adult porcine pancreatic cells. CONCLUSION: These data indicate that PDX-1, BETA2/NeuroD, and MafA facilitate the beta-cell differentiation of NPCCs, but not adult pig pancreatic cells. Therefore PDX-1, BETA2/NeuroD, and MafA-induced NPCCs can be considered good sources for the induction of pancreatic beta-cells, and may also have some utility in the treatment of diabetes.

EXPERIMENTAL RESEARCH OF EFFECT COMBINED WITH NEW RECOMBINANT HUMAN TUMOUR NECROSIS FACTOR AND ETOPOSIDE IN MURINE PNEUMOCELLULAR CARCINOMA / 肿瘤研究与临床

Objective To investigate the inhibitive effects of treatment with new recombinant humantumor necrosis factor (nrhTNF) and/or etoposide (VP16) on murine lung cancer. Methods Tumor-bearingmice were randomly divided into four groups. NS, nrhTNF, VP16, nrhTNF and VP16, were respectivelyinjected into endoneoplasm in every group. Results Inhibition rate in nrhTNF group and VP16 group were33.71 % and 30. 46% respectively and resulted in tumor necrosis to a certain degree. The number of lungmetastatic tumors in the mentioned groups above were less than that in control group (P

A Phase 2 Study of VP-16 , Ifosfamide , and Cisplatin ( VIP ) Combination Chemotherapy Plus Concurrent Thoracic Irradiation for Limited Small Cell Lung Cancer / 대한암학회지

PURPOSE: A phase II study of etoposide, ifosfamide, cisplatin combination chemotherapy and concurrent thoracic irradiation in patients with untreated limited small cell lung cancer (SCLC) was conducted to assess toxicities, response rate, response duration, and median survival. MATERIALS AND METHODS: Patients with histologically confirmed SCLC with a ECOG criteria 2 and adequate renal function and bone marrow reserve were eligible. Each cycle consisted of VP-16 100 mg/m i.v, days 1-3, ifosfamide 1,200 mg/m i.v. days 1-3 with Mesna, and cisplatin 30 mg/m i.v. days 1-3. Cycles were repeated every 21 days. Concutrent thoracic itradiation was given as total 40-45 Gy for 4-5 weeks beginning within 24 hours of the third cycle. Patients with complete remission received prophylactic cranial irradiation after the 6th cycle. RESULT: Forty two patients with limited SCLC were treated at Seoul National University Hospital between December 1993 and August 1996. Three patients were not evaluable because of lost to follow up (2 patients) and one treatment-related early death. Of 39 evaluable patients, responses were seen in 38 (97%) patients including 22 (56%) complete responses and 16 (41%) partial responses. The median remission duration was 65 wks. The median disease free survival was 60 wks. The median overall survival was not reached and 2-year survival was 69% with median duration of follow up of 63.5 wks. Hematologic side effects (WHO Gr>III/IV) of evaluable 228 cycles of chemotherapy were leukopenia in 34%, thrombocytopenia in 16%. One patient expired after prolonged leukopenia and sepsis. Nonhematologic side effects (WHO Gr>II) included nausea and vomiting (17%) and peripheral neuropathy (2%). CONCLUSION: VIP combination chemotherapy with concurrent thoracic irradiation is effective and tolerable in limited SCLC.

A Case of Gastric Kaposi's Sarcoma Successfully Treated with VP-16 / 대한소화기내시경학회지

Kaposi's sarcoma, a rare tumor, usually presents itself with skin lesions. However, extracutaneous lesions are common and the gastrointestinal tract is often involved. Gastric Kaposi's sarcoma is usually asymptomatic, but may cause massive gastrointestinal hemorrhage, perforation, intestinal obstruction, intussusception, protein-losing enteropathy, or sepsis. The gastroscopic appearances of Kaposi's sarcoma range from reddish purple maculopapules to polypoid, umbilicated nodules. In Korea, only one case of gastric Kaposi's sarcoma had been reported until now. A case of gastric Kaposi's sarcoma treated with VP-16 (etoposide) is here in reported with the endoscopic findings before and after chemotherapy.

Clinical observation of HEPP regimen in treatment of refractory Non-Hodgkin lymphoma / 肿瘤研究与临床

Objective To observe the short-term efficacy and toxicity of HEPP regimen in treatment of refractory Non-Hodgkin's Lymphoma. Methods HEPP regimen: HCPT 8 mg/m2 iv gtt d1~ d5, VP16 100 mg/d iv gtt d1~d5, PDD 20 mg/d iv gtt d1~d5, PDN 60 mg/m2 po d1~d14. The chemotherapy was repeated every 4 weeks as a cycle.The clinical effect was evaluated after 2 cycles and toxicity was observed during every cycle. Results 25 patients were eligible for toxicity evaluation and 22 patients for clinical response evaluation. The objective response rate was 60.0 %, including three cases complete remission and ten cases partial remission. Six cases achieved stable disease and three cases progressive disease. The major toxicity was bone marrow suppression, including 24.0 % grade Ⅲ/Ⅳ leukopenia and 12.0 % grade Ⅲ/Ⅳ thrombocytopenia. The incidence of nausea/vomiting, mucositis and hepatic toxicity was low. Conclusion HEPP regimen can achieve a satisfy result in the treatment of refractory Non-Hodgkin's Lymphoma. It is low toxic and well tolerated.

Combination Chemotherapy with Etoposide, Ifosfamide, and Cisplatin (VIP) in Small Cell Lung Cancer / 대한암학회지

PURPOSE: A prospective phase II trial was conducted in patients with small cell lung cancer (SCLC) to determine whether the response rate, duration of response, and overall survival can be improved by a combination chemotherapy with etoposide, ifosfamide, and cisplatin (VIP). MATERIALS AND METHODS: From May 1994 to April 1997, thirty-three previously untreated patients with SCLC received individualized treatment tailored to disease extent. Twenty-one patients with limited disease (LD) received six cycles of chemotherapy consisting of etoposide 120 mg/m2, ifosfamide 1,500 mg/m2, and cisplatin 25 mg/m2 all given intravenously on days 1, 3 and 5. Cycles were repeated every 3 weeks for six cycles. Thoracic radiotherapy was administered to 15 patients with LD of SCLC subsequently after initial two or three cycles of chemotherapy. Prophylactic cranial irradiation was given to complete responders of SCLC. Chemotherapy alone was administered to 12 patients with extensive disease (ED) of SCLC. RESULTS: Complete response (CR) rate was 51% (LD 67%, ED 25%) and overall response rate was 94% (LD 95%, ED 92, p=0.022). And the median duration of response of all patients was 8 months (11 months in LD, 6.5 months in ED, p=0.042). With a median follow-up period of 13 months (3+~36), the median survival of all patients was 12 months (16 months in LD, 9.5 months in ED, p=0.006), and the median disease-free survival (DFS) of 17 CR patients was 12 months. Stage and performance status score were important prognostic factor, but sex, age, and LDH level did not affect the outcome significantly. Among 21 patients with LD, 15 patients received radiotherapy and 6 did not. The overall response rate of patients who received radiotherapy was significantly higher than that of patients who did not (p=0.045). But there were no significant differences in duration of response and OS between them (p=0.055, p=0.068, respectively). The major side effects (greater than grade 2 of WHO criteria) of evaluable 154 cycles of chemotherapy were alopecia (76%), nausea/vomiting (54%), leukopenia (27%), anemia (19%), and thrombocytopenia (15%). CONCLUSION: VIP chemotherapy has produced a high complete remission rate and it is a safe and well-tolerated regimen in SCLC. However, compared to previous reports, it has not improved overall survival significantly. Further phase II and III studies are warranted to confirm the efficacy of VIP chemotherapy.

Neoadjuvant Quick Cisplatin-VP16 in High Risk Cervical Cancer / 대한산부인과학회잡지

The potential role and determinants of response to a cisplatin-based regimen of neoadju-vant chemotherapy in women with a histologically confirmed first diagnosis of stage IB-III cervical cancer were analyzed. From 1993 to 1996, 92 patients with bulky(designated as more than 3X3 cm2 size) mass were treated with cisplatin 60 mg/m2 and etoposide 100 mg/m2, admi-nistered intravenously at 7 day intervals. Seventy cases of radical hysterectomy with pelvic lymph node dissection and 22 cases of radiation therapy were performed 2 to 3 weeks after chemotherapy. At the end of the cycles, the overall clinical response rate of portio was 83.7 %(34.8 % with a complete response and 48.9 % with a partial response). The older ages, lower stages, and squamous cell types correlated favorably with the clinical response of the portio, but neither with the parametrium nor with the vagina. After the operation, we found the diff-erences in histologic responses, with the following parameters : lymphovascular space invasion, 3 mm below stromal invasion and lymph node metastasis. Theses parameters correlated with the clinical responses, and the down-staging of cases were 70 %. In comparison with radiolog-ical findings of pretreatment and postoperative tissue pathology, we could find a decrease in pelvic LN metastasis. The tumor-free survival rate calculated by the Kaplan-Meier product limit method was 75 % but it was 86.1 % for cases without the occurrence of persistent disease after the completion of the treatments. All patients suffered from nausea and vomiting, but grade 4 toxicity was not detected after the routine use of antiemetics. There were no events that delayed the next step in the treatment or caused difficulty during the operation. The results of this study suggest that the neoadjuvant chemotherapy should be accepted as a routine tool in treating high risk cervical cancer in order to improve the likelihood of favorable outcomes.

Anti-tumor activity of tumor necrosis factor alone and combination with VP-16 on renal cell carcinoma in a nude mice xenograft model / 대한비뇨기과학회지

Investigations of the anti-tumor activity of recombinant mouse TNF and etoposide(VP-16) in a nude mouse subcutaneous implantation xenograft model utilizing the CURC-1 human renal cell carcinoma cell line were performed. Recombinant mouse tumor necrosis factor-alpha(rTNF-alpha) and VP-16. both well known cytotoxic and cytostatic anticancer agents were evaluated singly and in combination against subcutaneously growing CURC-1. The results were as follows : 1. In the absence of treatment(Group I). subcutaneously growing CURC-1 tumor nodules demonstrated continued rapid growth. 2. Administration of rTNF(Group II) induced significant tumor regression in the subcutaneous nodules. 3. Administration of rTNF and Etoposide(Group III) demonstrated significant tumor growth inhibition. On histopathological findings, Group I (control) shows rare leukocyte infiltration and no tumor necrosis. In contrast, Group II shows tumor necrosis and more leukocyte infiltration than Group I . Group III demonstrates tumor necrosis. tumor cell degeneration and more leukocyte infiltration than Group II. These results suggest that TNF have antineoplastic effect against subcutaneous human renal cell carcinoma nodule but the synergistic effect of TNF with VP-l6 is uncertain.