During autologous bone marrow graft in treatment of malignant diseases, it is critical to purge malignant cells from the marrow. In the present study, the sensitivity to photodynamic inactivation of 3 leukemic cell li...During autologous bone marrow graft in treatment of malignant diseases, it is critical to purge malignant cells from the marrow. In the present study, the sensitivity to photodynamic inactivation of 3 leukemic cell lines was compared with their counterpart normal hematopoietic cells. After mouse leukemic L1210 cells were treated with a preparation of hematoporphyrin derivatives, YHpD, 10 μg/ml for 1 hr. and irradiated with blacklight (peak wavelength 395 nm, light intensity 0.6 mW/cm2) for 5 minutes, the survival rate of clonogenic cells decreased to <10%, while that of bone marrow granulocyte macrophage progenitor cells (CFU-GM) in DBA/2 mice remained at nearly normal level (>80%). Similar results were obtained when human leukemic HL-60 cells were compared with human CFU-GM and mouse leukemic L615 cells with CFU-GM in 615 strain mice. It is suggested that hematoporphyrin photoradiation may be useful for Iselectively killing leukemic cells in bone marrow.展开更多
Objective: To investigate the mechanism of carcinogenesis, invasion and metastasis. Methods: The expressions of adhesive molecule and adhesive structure in v-k-ras transformed normal rat kidney cells (KNRK) were d...Objective: To investigate the mechanism of carcinogenesis, invasion and metastasis. Methods: The expressions of adhesive molecule and adhesive structure in v-k-ras transformed normal rat kidney cells (KNRK) were detected with a variety of molecular biological techniques, including cell culture, immunofluorescence labeling, electron microscopy, polyacrylamide gel electrophoresis, and protein blotting, and compared with normal rat kidney (NRK) cells. Results: The significantly shortened doubling time, remarkably active proliferation ability in soft agar, and invasive growth in the abdomen of nude rat, demonstrated the malignant biological behaviors of KNRK cells. In KNRK cells, the adhesive molecules, P-cadherin, α and β catenin, actin, and adhesive structures, the adhesive junction and gap junction, were all abnormally expressed. And cell aggregation was significantly decreased. The aggregation ability disappeared at 20℃, and became active with a suitable amount of calcium solution. Conclusion: Following the transfection of virus K-ras gene, normal cells were transformed into malignant cells. In early stage of cancer, the variation of adhesive ability may be one of the vital factors underlying tumorigenesis, invasion and metastasis.展开更多
BACKGROUND Malignant small round cell tumor(MSRCT)metastasis to the common bile duct associated with recurrent biliary hemorrhage is extremely rare.Thus far,there have been no reports of metastatic small round cell tu...BACKGROUND Malignant small round cell tumor(MSRCT)metastasis to the common bile duct associated with recurrent biliary hemorrhage is extremely rare.Thus far,there have been no reports of metastatic small round cell tumors of the common bile duct.CASE SUMMARY Herein,we report the case of a 77-year-old female patient with an MSRCT in the common bile duct.The patient was admitted to hospital due to gastrointestinal hemorrhage and abdominal pain.We found a neoplasm in the common bile duct with active bleeding through a spyglass.We performed biopsy through the spyglass and placed a metal stent to stop bleeding.The pathological result suggested that it was an MSRCT metastasized from the back to the common bile duct.Later,we found using fluorescence in situ hybridization that the SS18 gene break test was negative,ruling out the diagnosis of synovial sarcoma.CONCLUSION MSRCT is a group of tumors with similar cell morphology and diffuse histological structure.Complete tumor resection results in improved survival in patients with MSRCT.Roux-en-Y cholangiojejunostomy was performed.After excision of the common bile duct tumor,the patient felt that the abdominal pain improved and hemorrhage disappeared.The patient underwent routine fecal examination one month after surgery,indicating a negative fecal occult blood test.On May 22,2023,the patient was reexamined by abdominal computed tomography,and no abdominal space occupying lesions or abdominal lymphadenopathy was found.展开更多
We have established an IL-2 independent malignant lymphoma line (CM-1) from peripheral T lymphocytes donated by a femalc patient with nervous systcm disease, the binlogical characteristics of CM-1 cells was studied in...We have established an IL-2 independent malignant lymphoma line (CM-1) from peripheral T lymphocytes donated by a femalc patient with nervous systcm disease, the binlogical characteristics of CM-1 cells was studied in this paper. Another T lymphocytes,such as peripheral T lymphocytes donated by a maIe patient with multiple sclerosis, could be transformed into a malignant lymphoma line by using filtered supernatant of the CM-1 cultured medium, thus the CM-2 cell line u'as estabIished. The CM-1 and CM-2 cells were transplanted by subcutaneous inoculation into nude mice, and could cause the occurrenceof typical maIignant lymphoma. The observation of eIectron micrographs suggested the existence of virions in the CM-1 and CM-2 cells, and these virions were similar toretrovirus in the ultra-structure characteristics. lt was found that this virus possesses reverse transcriptase activity. ResuIts obtained from serological assay, molecular hybridization and PCR excluded the existence of other human viruses, which were commonly usedin our laboratory. The unknown virus possesses strong transformation activity, and probably is a new retro virus. Meanwhile, the work on the clone and sequence analysis ofthis virus are being carried out.展开更多
Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresul...Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-展开更多
Objective: To investigate the F1t3 receptor expression on the surface of malignant hematopoietic cells, the effect of TNFα and dexamethasone (DXM) on its expression and the responses of those cells to recombinant hum...Objective: To investigate the F1t3 receptor expression on the surface of malignant hematopoietic cells, the effect of TNFα and dexamethasone (DXM) on its expression and the responses of those cells to recombinant human F1t3 ligand (rhFL). Methods: Eighteen malignant hematopoietic cell lines were determined for the F1t3 receptor expression by flow cytometric analysis. The effect of rhFL on the proliferation of malignant hematopoietic cellsin vitro was measured using MTT assay. Results: The expressions of F1t3 receptor on the surface of Raji, Daudi, HL-60, 8266 and XG-6 cells were detected by flow cytometric analysis. Following incubation with 20 ng/ml TNFα for 24h, the number of F1t3 receptor positive cells decreased in Raji and 8266, increased in HL-60 and XG-6, and no difference in Daudi cells. After incubation with 10?6 mol/L DXM for 24h, the number of F1t3 receptor positive cells decreased in all the 5 F1t3 receptor positive cell lines. rhFL stimulated the proliferation of HL-60 and Raji cells. Conclusion: For most of the malignant hematopoietic cells, there was neither the expression of F1t3 receptor nor the response to rhFL. DXM may be useful to reduce the effect of FL on the proliferation of some F1t3 receptor positive malignant hematopoietic cells in vitro andin vivo.展开更多
We developed a serum-free culture system that promoted the growth of B cell colonies in peripheral blood, bone marrow, lymph nodes and cerebrospinal fluid (CSF) from 7 out of 8 patients with non-Hodgkin's lymphoma...We developed a serum-free culture system that promoted the growth of B cell colonies in peripheral blood, bone marrow, lymph nodes and cerebrospinal fluid (CSF) from 7 out of 8 patients with non-Hodgkin's lymphomas of B cell type. The culture cells were pretreated with or without galactose oxi-dase (GO) prior to plating. Colony growth was best supported with BCGF. A moderate increment was observed with rIL-3, as well as rIL-1β and even to a lesser degree, by rlL-2, while B cell stimulating factor-2 (rBCSF-2) and rlL-1β did not show significant activity. rGM-CSF and rG-CSF had little effect, while rM-CSF enhanced the formation of lymphoma colonies. The cells from different patients had different requirements for Staphylococcus aureus protein A and GO pretreatment. It reflected the differences in activation and differentiation status and surface properties of lymphoma cells from different patients. The cells from CSF of one patient were successfully maintained in serum-free culture medium supplemented with 10% BCGF or 5% PHA-LCM for more than 4 months. The long-term culture cells were EBV negative, phenotypically consistent with B cells and gene rearrangements for JH, Kappa and myc. This serum-free culture system allowed extensive analysis of the growth requirements for clonogenic precursors.展开更多
BACKGROUND Malignant ovarian germ cell tumors(MOGCT)are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after fertility-sparing surgery(FSS)for this disease...BACKGROUND Malignant ovarian germ cell tumors(MOGCT)are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after fertility-sparing surgery(FSS)for this disease are still limited.AIM To evaluate the oncology and reproductive outcomes of MOGCT patients who underwent FSS.METHODS All MOGCT patients who underwent FSS defined as the operation with a preserved uterus and at least one side of the ovary at our institute between January 2005 and December 2020 were retrospectively reviewed.RESULTS Sixty-two patients were recruited for this study.The median age was 22 years old and over 77%were nulliparous.The three most common histology findings were immature teratoma(32.2%),dysgerminoma(24.2%),and yolk sac tumor(24.2%).The distribution of stage was as follows;Stage I,74.8%;stage II,9.7%;stage III,11.3%;and stage IV,4.8%.Forty-three(67.7%)patients received adjuvant chemotherapy.With a median follow-up time of 96.3 mo,the 10-year progressionfree survival and overall survival were 82.4%and 91%,respectively.For reproductive outcomes,of 43 patients who received adjuvant chemotherapy,18(41.9%)had normal menstruation,and 17(39.5%)resumed menstruation with a median time of 4 mo.Of about 14 patients who desired to conceive,four were pregnant and delivered good outcomes.Only one case was aborted.Therefore,the successful pregnancy rate was 28.6%CONCLUSION The oncology and reproductive outcomes of MOGCT treated by FSS are excellent.Many patients show a long survival time with normal menstruation.However,the obstetric outcome is not quite satisfactory.展开更多
<strong>Background</strong><span style="font-family:Verdana;"><strong>:</strong></span><b><span style="font-family:""> </span></b>&l...<strong>Background</strong><span style="font-family:Verdana;"><strong>:</strong></span><b><span style="font-family:""> </span></b><span style="font-family:""><span style="font-family:Verdana;">Malignant granular cell tumor (GCT) is extremely rare. Malignant GCT with EP300 gene mutation in the bladder has not been reported in the literature. </span><b><span style="font-family:Verdana;">Case Presentation</span></b></span><b><span style="font-family:Verdana;">:</span></b><span style="font-family:""><span style="font-family:Verdana;"> We report a special case of 45-year-old female with malignant GCT of the bladder. Pathological examination showed that the mass was 11 × 11 × 4.5 cm in size, involved in the bladder’s posterior wall. Under the microscope, the tumor cells were arranged in the shape of a nest or cord to infiltrate the bladder’s wall. The tumor cells were pleomorphic, red-stained granular within the cytoplasm, with increased nuclear/cyto</span><span style="font-family:Verdana;">plasmic ratio, vacuolar nuclei, and obvious nucleoli. The tumor cells were</span> <span style="font-family:Verdana;">showed obvious nuclear atypia, and the mitosis was more than 5/50HPF. </span><span style="font-family:Verdana;">Coagulative necrosis was widely showed within the tumor. Immunohistochemi</span><span><span style="font-family:Verdana;">stry (IHC) showed that S-100, NSE, CD68, CR, </span><i><span style="font-family:Verdana;">α</span></i><span style="font-family:Verdana;">-AT, and TFE-3 were</span></span><span style="font-family:Verdana;"> strongly </span><span style="font-family:Verdana;">positive, and the Ki-67 proliferation index was around 15%. The</span><span style="font-family:Verdana;"> next-genera</span><span style="font-family:Verdana;">tion high throughput sequencing indicated that EP300 gene was missense</span><span style="font-family:Verdana;"> mutated (c.457A > G) with 33% mutation abundance, and genes of DPYD (c.1627A > G), ERCC1 (c.354T > C), NQO1 (c.559C > T), TPMT (c.719A > G) and XRCC1 (c.1196A > G) were polymorphic mutated. The patient died after three months of the second surgical treatment. </span><b><span style="font-family:Verdana;">Conclusions</span></b></span><b><span style="font-family:Verdana;">:</span></b><b><span style="font-family:""> </span></b><span style="font-family:Verdana;">We report for the first time a primary bladder malignant GCM accompanied by mutations in special driving genes such as EP300. We also conducted a comprehensive literature review and an in-depth discussion.</span>展开更多
To observe the process of invasion, retina of rat was used as a model to substitute the inner limiting membrane of retina for the basement membrane. Retina invaded by esophageal carcinoma cells and B16 melanoma cells ...To observe the process of invasion, retina of rat was used as a model to substitute the inner limiting membrane of retina for the basement membrane. Retina invaded by esophageal carcinoma cells and B16 melanoma cells upon the inner limiting membrane was studied by scanning and transmission electron microscopy. The results showed that the inner limiting membrane was destroyed by both kinds of tumor cells. The process of destruction was followed by a series of transformations in the inner limiting membrane, i.e. folding, swelling, thickening, and granular change. The inner limiting membrane was dissolved focally as a result of transformation, and then tumor cells invaded the retina through these dissolved regions. It seems that, as a barrier, the inner limiting membrane plays a similar role as the basement membrane.展开更多
Malignant transformation of hamsterembryo cells was induced in vitro by rareearth iron mineral dusts(MP),naturalthorium(Th02) and MP plus Th02.Dusts of MP,MP plus Th02 or Th02 were added into themedium with the final ...Malignant transformation of hamsterembryo cells was induced in vitro by rareearth iron mineral dusts(MP),naturalthorium(Th02) and MP plus Th02.Dusts of MP,MP plus Th02 or Th02 were added into themedium with the final concentration of 17.0,展开更多
Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35...Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35 patients P 】 50 years with malignant hematological diseases received allogeneic hematopoietic展开更多
Objective: To observe the expression of mouse Tbx2 gene in normal and malignant melanophore. Methods: The normal and malignant cells were used to extract total RNA. The expression of the Tbx2 gene was detected by RT-P...Objective: To observe the expression of mouse Tbx2 gene in normal and malignant melanophore. Methods: The normal and malignant cells were used to extract total RNA. The expression of the Tbx2 gene was detected by RT-PCR. Results: No expression of the Tbx2 gene in the normal melanocytes was noted, but all malignant cells showed expression of the Tbx2 gene. Conclusion: Tbx2 plays a critical role during the development of the malignant cells.展开更多
Objective: To evaluate the effect of Cx43 gene on gap junction intercellular communication (GJIC) and proliferation of glioma cells. Methods: Cx43 cDNA was transfected into TJ905 human glioblastoma cells using lipofec...Objective: To evaluate the effect of Cx43 gene on gap junction intercellular communication (GJIC) and proliferation of glioma cells. Methods: Cx43 cDNA was transfected into TJ905 human glioblastoma cells using lipofectamine. The expression of Cx43 was identified by Northern blot analyses, in situ hybridization and immunohistochemistry. MTT assay and average number of AgNORs (Argyrophlic nuclear organizer regions) were used to determine the cell proliferation. TUNEL method was used for detection of cell apoptosis, and scrape loading and dye tranfer method for examination of GJIC. Results: The Cx43 expression was greatly upregulated when Cx43 gene was transfected into TJ905 glioma cells. The cell proliferation was inhibited while the cell apoptosis was not increased and GJIC was significantly restored in the glioma cells transfected with Cx43 gene. Conclusion: Cx43 gene has an inhibitory effect on the glioma cell proliferation, but no effect on induction of cell apoptosis. The restoration of GJIC may be the major mechanism involved in its effect. Cx43 gene can be the candidate for gene therapy of gliomas.展开更多
Objective: HOXB7 gene is a kind of transcription regulator over-expressed in malignant melanoma (MM) cell lines. It can specifically up-regulate the expression of angiogenic factors and tumor growth factors such as...Objective: HOXB7 gene is a kind of transcription regulator over-expressed in malignant melanoma (MM) cell lines. It can specifically up-regulate the expression of angiogenic factors and tumor growth factors such as bFGF, GROa, VEGF and induce angiogenesis in melanoma, resulting in the proliferation and metastasis of tumor cells. We designed and synthesized HOXB7 specific siRNA to study its interfering effect on the expressions of HOXB7 and bFGF genes in melanoma A375 cell line and the biologic characteristics of A375 cells. Methods: Three synthesized siRNA with different sequences were separately transfected into A375 cells by lipofecter 2000. The expression of HOXB7 and bFGF mRNA in transfected cells was detected by RT-PCR 24 and 48 hours after transduction. The expression of bFGF protein in the transfected cells were detected by flowcytometry 48 hours after transfection. MTT assay was used to analyze the cell proliferation rate of siRNA transfected cells. Based on the in vitro experiment results, one effective siRNA sequence was selected for the construction of in vivo siRNA expression vector. Then, a malignant melanoma animal model was established. The siRNA expression plasmid was injected into the tumor foci and its influence on the growth and angiogenesis of tumor was observed. Results: The mRNA expressions of both HOXB7 and bFGF genes in the A375 cells reduced significantly 24 and 48 hour after transfection of siRNA. Expression level of the protein of angiogenic factor bFGF induced by HOXB7 gene in siRNA transfected cells was significantly lower than that in control cells 48 hours after transduction. Cell proliferation was also suppressed in siRNA transfected cells. Two of the three siRNA strands showed prominent interference effect. The in vivo study indicated that the tumor size and the microvessel density in the tumor both reduced after injection of HOXB7siRNA plasmid. Conclusion: Down-regulation of HOXB7 gene expression can effectively reduce the expression of angiogenic factor bFGF and the proliferation of MM cells. Besides, the growth and angiogenesis of MM tumor were also inhibited.展开更多
Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)...Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is unsatisfactory.Moreover,fatal side effects greatly impede CAR T cell application.Extracellular vesicles(EVs)are excellent carriers of therapeutic agents.Nevertheless,EVs mainly accumulate in the liver when administered without modification.As an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B cells.Here,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage electroporation.The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to RBC-EVs.After the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,respectively.Moreover,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal Bcells.Therefore,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.展开更多
Background:The aim of this study was to review clinical features of adolescent malignant germ cell tumors(MGCTs)in Beijing and analyze the peculiar characteristics of this age group.Methods:Clinical characteristics,pa...Background:The aim of this study was to review clinical features of adolescent malignant germ cell tumors(MGCTs)in Beijing and analyze the peculiar characteristics of this age group.Methods:Clinical characteristics,pathological presentations,and survival outcomes of 34 patients were analyzed retrospectively.Results:Of 34 patients,12 girls and 22 boys,18(52.9%)had an extra-cranial tumor,including one testicular tumor,five ovarian tumors,one sacrococcygeal tumor,and 11 mediastinal tumors.Histologically,we found immature teratomas(n=6),yolk sac tumors(n=5),mixed malignant tumors(n=5),an embryonic carcinoma(n=1),and seminoma(n=1).Three-year event-free survival(EFS)and overall survival(OS)were 48.8%and 62.9%,respectively.Another 16(47.1%)patients had an intracranial tumor,including nine in the pineal region,five in the suprasellar region,one in basal ganglia,and one in cerebellopontine.All patients had localized disease and an excellent outcome with 3-year EFS and OS of 93.7%and 100%,respectively.Conclusions:Adolescent MGCTs are rare with a strong dependence on gender,and the mediastina and pineal region are the most common tumor locations.The prognosis is promising compared with that of other adolescent tumors and MGCTs in other age groups.MGCTs in mediastina have a tendency to companion with other hematological malignancies,and the prognosis is extremely poor in these patients.展开更多
The matrix-degrading metalloproteinases (MMPs), particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant gliom...The matrix-degrading metalloproteinases (MMPs), particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA (pcDNA-AS-MMP9), which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex (AS-MMP-9-treated group), subcutaneous injection of endostatin (endostatin-treated group), or both (combined therapy group). Mice treated with pcDNA (empty vector)-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.展开更多
文摘During autologous bone marrow graft in treatment of malignant diseases, it is critical to purge malignant cells from the marrow. In the present study, the sensitivity to photodynamic inactivation of 3 leukemic cell lines was compared with their counterpart normal hematopoietic cells. After mouse leukemic L1210 cells were treated with a preparation of hematoporphyrin derivatives, YHpD, 10 μg/ml for 1 hr. and irradiated with blacklight (peak wavelength 395 nm, light intensity 0.6 mW/cm2) for 5 minutes, the survival rate of clonogenic cells decreased to <10%, while that of bone marrow granulocyte macrophage progenitor cells (CFU-GM) in DBA/2 mice remained at nearly normal level (>80%). Similar results were obtained when human leukemic HL-60 cells were compared with human CFU-GM and mouse leukemic L615 cells with CFU-GM in 615 strain mice. It is suggested that hematoporphyrin photoradiation may be useful for Iselectively killing leukemic cells in bone marrow.
基金This work was supported by the National Natural Sciences Foundation of China (No. 30371624).
文摘Objective: To investigate the mechanism of carcinogenesis, invasion and metastasis. Methods: The expressions of adhesive molecule and adhesive structure in v-k-ras transformed normal rat kidney cells (KNRK) were detected with a variety of molecular biological techniques, including cell culture, immunofluorescence labeling, electron microscopy, polyacrylamide gel electrophoresis, and protein blotting, and compared with normal rat kidney (NRK) cells. Results: The significantly shortened doubling time, remarkably active proliferation ability in soft agar, and invasive growth in the abdomen of nude rat, demonstrated the malignant biological behaviors of KNRK cells. In KNRK cells, the adhesive molecules, P-cadherin, α and β catenin, actin, and adhesive structures, the adhesive junction and gap junction, were all abnormally expressed. And cell aggregation was significantly decreased. The aggregation ability disappeared at 20℃, and became active with a suitable amount of calcium solution. Conclusion: Following the transfection of virus K-ras gene, normal cells were transformed into malignant cells. In early stage of cancer, the variation of adhesive ability may be one of the vital factors underlying tumorigenesis, invasion and metastasis.
文摘BACKGROUND Malignant small round cell tumor(MSRCT)metastasis to the common bile duct associated with recurrent biliary hemorrhage is extremely rare.Thus far,there have been no reports of metastatic small round cell tumors of the common bile duct.CASE SUMMARY Herein,we report the case of a 77-year-old female patient with an MSRCT in the common bile duct.The patient was admitted to hospital due to gastrointestinal hemorrhage and abdominal pain.We found a neoplasm in the common bile duct with active bleeding through a spyglass.We performed biopsy through the spyglass and placed a metal stent to stop bleeding.The pathological result suggested that it was an MSRCT metastasized from the back to the common bile duct.Later,we found using fluorescence in situ hybridization that the SS18 gene break test was negative,ruling out the diagnosis of synovial sarcoma.CONCLUSION MSRCT is a group of tumors with similar cell morphology and diffuse histological structure.Complete tumor resection results in improved survival in patients with MSRCT.Roux-en-Y cholangiojejunostomy was performed.After excision of the common bile duct tumor,the patient felt that the abdominal pain improved and hemorrhage disappeared.The patient underwent routine fecal examination one month after surgery,indicating a negative fecal occult blood test.On May 22,2023,the patient was reexamined by abdominal computed tomography,and no abdominal space occupying lesions or abdominal lymphadenopathy was found.
文摘We have established an IL-2 independent malignant lymphoma line (CM-1) from peripheral T lymphocytes donated by a femalc patient with nervous systcm disease, the binlogical characteristics of CM-1 cells was studied in this paper. Another T lymphocytes,such as peripheral T lymphocytes donated by a maIe patient with multiple sclerosis, could be transformed into a malignant lymphoma line by using filtered supernatant of the CM-1 cultured medium, thus the CM-2 cell line u'as estabIished. The CM-1 and CM-2 cells were transplanted by subcutaneous inoculation into nude mice, and could cause the occurrenceof typical maIignant lymphoma. The observation of eIectron micrographs suggested the existence of virions in the CM-1 and CM-2 cells, and these virions were similar toretrovirus in the ultra-structure characteristics. lt was found that this virus possesses reverse transcriptase activity. ResuIts obtained from serological assay, molecular hybridization and PCR excluded the existence of other human viruses, which were commonly usedin our laboratory. The unknown virus possesses strong transformation activity, and probably is a new retro virus. Meanwhile, the work on the clone and sequence analysis ofthis virus are being carried out.
文摘Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-
文摘Objective: To investigate the F1t3 receptor expression on the surface of malignant hematopoietic cells, the effect of TNFα and dexamethasone (DXM) on its expression and the responses of those cells to recombinant human F1t3 ligand (rhFL). Methods: Eighteen malignant hematopoietic cell lines were determined for the F1t3 receptor expression by flow cytometric analysis. The effect of rhFL on the proliferation of malignant hematopoietic cellsin vitro was measured using MTT assay. Results: The expressions of F1t3 receptor on the surface of Raji, Daudi, HL-60, 8266 and XG-6 cells were detected by flow cytometric analysis. Following incubation with 20 ng/ml TNFα for 24h, the number of F1t3 receptor positive cells decreased in Raji and 8266, increased in HL-60 and XG-6, and no difference in Daudi cells. After incubation with 10?6 mol/L DXM for 24h, the number of F1t3 receptor positive cells decreased in all the 5 F1t3 receptor positive cell lines. rhFL stimulated the proliferation of HL-60 and Raji cells. Conclusion: For most of the malignant hematopoietic cells, there was neither the expression of F1t3 receptor nor the response to rhFL. DXM may be useful to reduce the effect of FL on the proliferation of some F1t3 receptor positive malignant hematopoietic cells in vitro andin vivo.
文摘We developed a serum-free culture system that promoted the growth of B cell colonies in peripheral blood, bone marrow, lymph nodes and cerebrospinal fluid (CSF) from 7 out of 8 patients with non-Hodgkin's lymphomas of B cell type. The culture cells were pretreated with or without galactose oxi-dase (GO) prior to plating. Colony growth was best supported with BCGF. A moderate increment was observed with rIL-3, as well as rIL-1β and even to a lesser degree, by rlL-2, while B cell stimulating factor-2 (rBCSF-2) and rlL-1β did not show significant activity. rGM-CSF and rG-CSF had little effect, while rM-CSF enhanced the formation of lymphoma colonies. The cells from different patients had different requirements for Staphylococcus aureus protein A and GO pretreatment. It reflected the differences in activation and differentiation status and surface properties of lymphoma cells from different patients. The cells from CSF of one patient were successfully maintained in serum-free culture medium supplemented with 10% BCGF or 5% PHA-LCM for more than 4 months. The long-term culture cells were EBV negative, phenotypically consistent with B cells and gene rearrangements for JH, Kappa and myc. This serum-free culture system allowed extensive analysis of the growth requirements for clonogenic precursors.
文摘BACKGROUND Malignant ovarian germ cell tumors(MOGCT)are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after fertility-sparing surgery(FSS)for this disease are still limited.AIM To evaluate the oncology and reproductive outcomes of MOGCT patients who underwent FSS.METHODS All MOGCT patients who underwent FSS defined as the operation with a preserved uterus and at least one side of the ovary at our institute between January 2005 and December 2020 were retrospectively reviewed.RESULTS Sixty-two patients were recruited for this study.The median age was 22 years old and over 77%were nulliparous.The three most common histology findings were immature teratoma(32.2%),dysgerminoma(24.2%),and yolk sac tumor(24.2%).The distribution of stage was as follows;Stage I,74.8%;stage II,9.7%;stage III,11.3%;and stage IV,4.8%.Forty-three(67.7%)patients received adjuvant chemotherapy.With a median follow-up time of 96.3 mo,the 10-year progressionfree survival and overall survival were 82.4%and 91%,respectively.For reproductive outcomes,of 43 patients who received adjuvant chemotherapy,18(41.9%)had normal menstruation,and 17(39.5%)resumed menstruation with a median time of 4 mo.Of about 14 patients who desired to conceive,four were pregnant and delivered good outcomes.Only one case was aborted.Therefore,the successful pregnancy rate was 28.6%CONCLUSION The oncology and reproductive outcomes of MOGCT treated by FSS are excellent.Many patients show a long survival time with normal menstruation.However,the obstetric outcome is not quite satisfactory.
文摘<strong>Background</strong><span style="font-family:Verdana;"><strong>:</strong></span><b><span style="font-family:""> </span></b><span style="font-family:""><span style="font-family:Verdana;">Malignant granular cell tumor (GCT) is extremely rare. Malignant GCT with EP300 gene mutation in the bladder has not been reported in the literature. </span><b><span style="font-family:Verdana;">Case Presentation</span></b></span><b><span style="font-family:Verdana;">:</span></b><span style="font-family:""><span style="font-family:Verdana;"> We report a special case of 45-year-old female with malignant GCT of the bladder. Pathological examination showed that the mass was 11 × 11 × 4.5 cm in size, involved in the bladder’s posterior wall. Under the microscope, the tumor cells were arranged in the shape of a nest or cord to infiltrate the bladder’s wall. The tumor cells were pleomorphic, red-stained granular within the cytoplasm, with increased nuclear/cyto</span><span style="font-family:Verdana;">plasmic ratio, vacuolar nuclei, and obvious nucleoli. The tumor cells were</span> <span style="font-family:Verdana;">showed obvious nuclear atypia, and the mitosis was more than 5/50HPF. </span><span style="font-family:Verdana;">Coagulative necrosis was widely showed within the tumor. Immunohistochemi</span><span><span style="font-family:Verdana;">stry (IHC) showed that S-100, NSE, CD68, CR, </span><i><span style="font-family:Verdana;">α</span></i><span style="font-family:Verdana;">-AT, and TFE-3 were</span></span><span style="font-family:Verdana;"> strongly </span><span style="font-family:Verdana;">positive, and the Ki-67 proliferation index was around 15%. The</span><span style="font-family:Verdana;"> next-genera</span><span style="font-family:Verdana;">tion high throughput sequencing indicated that EP300 gene was missense</span><span style="font-family:Verdana;"> mutated (c.457A > G) with 33% mutation abundance, and genes of DPYD (c.1627A > G), ERCC1 (c.354T > C), NQO1 (c.559C > T), TPMT (c.719A > G) and XRCC1 (c.1196A > G) were polymorphic mutated. The patient died after three months of the second surgical treatment. </span><b><span style="font-family:Verdana;">Conclusions</span></b></span><b><span style="font-family:Verdana;">:</span></b><b><span style="font-family:""> </span></b><span style="font-family:Verdana;">We report for the first time a primary bladder malignant GCM accompanied by mutations in special driving genes such as EP300. We also conducted a comprehensive literature review and an in-depth discussion.</span>
文摘To observe the process of invasion, retina of rat was used as a model to substitute the inner limiting membrane of retina for the basement membrane. Retina invaded by esophageal carcinoma cells and B16 melanoma cells upon the inner limiting membrane was studied by scanning and transmission electron microscopy. The results showed that the inner limiting membrane was destroyed by both kinds of tumor cells. The process of destruction was followed by a series of transformations in the inner limiting membrane, i.e. folding, swelling, thickening, and granular change. The inner limiting membrane was dissolved focally as a result of transformation, and then tumor cells invaded the retina through these dissolved regions. It seems that, as a barrier, the inner limiting membrane plays a similar role as the basement membrane.
文摘Malignant transformation of hamsterembryo cells was induced in vitro by rareearth iron mineral dusts(MP),naturalthorium(Th02) and MP plus Th02.Dusts of MP,MP plus Th02 or Th02 were added into themedium with the final concentration of 17.0,
文摘Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35 patients P 】 50 years with malignant hematological diseases received allogeneic hematopoietic
文摘Objective: To observe the expression of mouse Tbx2 gene in normal and malignant melanophore. Methods: The normal and malignant cells were used to extract total RNA. The expression of the Tbx2 gene was detected by RT-PCR. Results: No expression of the Tbx2 gene in the normal melanocytes was noted, but all malignant cells showed expression of the Tbx2 gene. Conclusion: Tbx2 plays a critical role during the development of the malignant cells.
基金This work was supported by the National Natural Science Foundation of China (No. 39870815).
文摘Objective: To evaluate the effect of Cx43 gene on gap junction intercellular communication (GJIC) and proliferation of glioma cells. Methods: Cx43 cDNA was transfected into TJ905 human glioblastoma cells using lipofectamine. The expression of Cx43 was identified by Northern blot analyses, in situ hybridization and immunohistochemistry. MTT assay and average number of AgNORs (Argyrophlic nuclear organizer regions) were used to determine the cell proliferation. TUNEL method was used for detection of cell apoptosis, and scrape loading and dye tranfer method for examination of GJIC. Results: The Cx43 expression was greatly upregulated when Cx43 gene was transfected into TJ905 glioma cells. The cell proliferation was inhibited while the cell apoptosis was not increased and GJIC was significantly restored in the glioma cells transfected with Cx43 gene. Conclusion: Cx43 gene has an inhibitory effect on the glioma cell proliferation, but no effect on induction of cell apoptosis. The restoration of GJIC may be the major mechanism involved in its effect. Cx43 gene can be the candidate for gene therapy of gliomas.
基金the grants from the Research Foundation of Science & Technology Bureau of Guangzhou(2004Z2-E0011)the Guangdong Province Natural Science Foundation(5002318)
文摘Objective: HOXB7 gene is a kind of transcription regulator over-expressed in malignant melanoma (MM) cell lines. It can specifically up-regulate the expression of angiogenic factors and tumor growth factors such as bFGF, GROa, VEGF and induce angiogenesis in melanoma, resulting in the proliferation and metastasis of tumor cells. We designed and synthesized HOXB7 specific siRNA to study its interfering effect on the expressions of HOXB7 and bFGF genes in melanoma A375 cell line and the biologic characteristics of A375 cells. Methods: Three synthesized siRNA with different sequences were separately transfected into A375 cells by lipofecter 2000. The expression of HOXB7 and bFGF mRNA in transfected cells was detected by RT-PCR 24 and 48 hours after transduction. The expression of bFGF protein in the transfected cells were detected by flowcytometry 48 hours after transfection. MTT assay was used to analyze the cell proliferation rate of siRNA transfected cells. Based on the in vitro experiment results, one effective siRNA sequence was selected for the construction of in vivo siRNA expression vector. Then, a malignant melanoma animal model was established. The siRNA expression plasmid was injected into the tumor foci and its influence on the growth and angiogenesis of tumor was observed. Results: The mRNA expressions of both HOXB7 and bFGF genes in the A375 cells reduced significantly 24 and 48 hour after transfection of siRNA. Expression level of the protein of angiogenic factor bFGF induced by HOXB7 gene in siRNA transfected cells was significantly lower than that in control cells 48 hours after transduction. Cell proliferation was also suppressed in siRNA transfected cells. Two of the three siRNA strands showed prominent interference effect. The in vivo study indicated that the tumor size and the microvessel density in the tumor both reduced after injection of HOXB7siRNA plasmid. Conclusion: Down-regulation of HOXB7 gene expression can effectively reduce the expression of angiogenic factor bFGF and the proliferation of MM cells. Besides, the growth and angiogenesis of MM tumor were also inhibited.
基金supported by the Natural Science Foundation of Zhejiang Province(LY19H160009 and LY20H120007)the National Natural Science Foundation of China(82130053,81971871,31970845 and 81901571)+1 种基金the Joint Preresearch Fund for Clinical Scientific Research of Hangzhou First People’s Hospital Affiliated to Zhejiang University(YYJJ2019Z07)the Major Project of Hangzhou Health Science and Technology Plan(Z20200134).
文摘Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is unsatisfactory.Moreover,fatal side effects greatly impede CAR T cell application.Extracellular vesicles(EVs)are excellent carriers of therapeutic agents.Nevertheless,EVs mainly accumulate in the liver when administered without modification.As an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B cells.Here,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage electroporation.The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to RBC-EVs.After the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,respectively.Moreover,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal Bcells.Therefore,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.
文摘Background:The aim of this study was to review clinical features of adolescent malignant germ cell tumors(MGCTs)in Beijing and analyze the peculiar characteristics of this age group.Methods:Clinical characteristics,pathological presentations,and survival outcomes of 34 patients were analyzed retrospectively.Results:Of 34 patients,12 girls and 22 boys,18(52.9%)had an extra-cranial tumor,including one testicular tumor,five ovarian tumors,one sacrococcygeal tumor,and 11 mediastinal tumors.Histologically,we found immature teratomas(n=6),yolk sac tumors(n=5),mixed malignant tumors(n=5),an embryonic carcinoma(n=1),and seminoma(n=1).Three-year event-free survival(EFS)and overall survival(OS)were 48.8%and 62.9%,respectively.Another 16(47.1%)patients had an intracranial tumor,including nine in the pineal region,five in the suprasellar region,one in basal ganglia,and one in cerebellopontine.All patients had localized disease and an excellent outcome with 3-year EFS and OS of 93.7%and 100%,respectively.Conclusions:Adolescent MGCTs are rare with a strong dependence on gender,and the mediastina and pineal region are the most common tumor locations.The prognosis is promising compared with that of other adolescent tumors and MGCTs in other age groups.MGCTs in mediastina have a tendency to companion with other hematological malignancies,and the prognosis is extremely poor in these patients.
基金supported by the National Natural Science Foundation of China(30770827,31170864and81100887)National Basic Research Development Program of China(973Program,2010CB529405)+5 种基金Key Laboratory Project of Tianjin Municipality for Science and Technology(10SYSYJC28800)Major Program of Research on Applied Fundamentals and Frontier Technologies(10JCZDJC19400)Key Program of Higher Education of Tianjin Municipality for Science and Technology(2004ZD06,20060202)Program for New Century Excellent Talents in University of China(NCET-11-1067)Key Project of Natural Science Foundation of Tianjin Municipality,China(12JCZDJC24200)Key Project for Science and Technology of Ministry of Education,China(212005)
文摘The matrix-degrading metalloproteinases (MMPs), particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA (pcDNA-AS-MMP9), which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex (AS-MMP-9-treated group), subcutaneous injection of endostatin (endostatin-treated group), or both (combined therapy group). Mice treated with pcDNA (empty vector)-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.