Farah Zia - Academia.edu (original) (raw)
Papers by Farah Zia
PubMed, Nov 1, 1993
The effect of thymosin alpha 1 (THN alpha 1) and its NH2-terminal fragment (THN1-14) and COOH-ter... more The effect of thymosin alpha 1 (THN alpha 1) and its NH2-terminal fragment (THN1-14) and COOH-terminal fragment (THN15-28) on non-small cell lung cancer (NSCLC) growth was evaluated. Using an anti-THN alpha 1 antibody, receptors were identified on NSCLC cells that were pretreated with 10(-6) M THN alpha 1. [3H]Arachidonic acid was readily taken up by NSCLC cells and THN alpha 1 significantly increased the rate of arachidonic acid release. THN1-15 slightly stimulated but THN15-28 and THN beta 4 did not alter arachidonic acid release from NCI-H1299 cells. In clonogenic growth assays in vitro, THN alpha 1 (10(-6) M) significantly decreased NSCLC colony number whereas THN1-14, THN15-28, and THN beta 4 were less potent. Using growth assays in vivo, THN alpha 1 (10 micrograms s.c./day) but not THN1-14, THN15-28, or THN beta 4 inhibited significantly NSCLC xenograft formation in nude mice. These data suggest that biologically active THN alpha 1 receptors are present on NSCLC cells and that native THN alpha 1 inhibits the growth of human NSCLC.
Annals of the New York Academy of Sciences, Jan 25, 2006
VIP/PACAP are autocrine growth factors for lung cancer. VIP and/or PACAP mRNA is present in most ... more VIP/PACAP are autocrine growth factors for lung cancer. VIP and/or PACAP mRNA is present in most lung cancer cell lines examined. Although mRNA for VPAC2-R is not common, VPAC1-R and PAC1-R mRNA is present in many lung cancer cell lines. 125I-VIP binds with high affinity to lung cancer cells and specific 125I-VIP binding is inhibited with high affinity by (Lys15, Arg16, Leu27)VIP1-7 GRF8-27, the VPAC1-R specific agonist, but not by Ro25-1553(18), the VPAC2-R specific agonist. VIP elevates cAMP and increases c-fos gene expression. The increase in cAMP and c-fos mRNA caused by VIP is inhibited by SN(VH). (SH)VH inhibited the proliferation of NCIH1299 cells in the MTT assay, which is based on cytotoxicity. In a recent cell line screen, (SN)VH inhibited the growth of 51 of 56 cancer cell lines including leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, breast cancer, and prostate cancer (T. Moody, unpublished). It remains to be determined if (SN)VH will be useful for treatment of a wide variety of cancers.
PubMed, 1992
The ability of monoclonal antibody (MAb 108), an immunoglobulin G (IgG)2a against the epidermal g... more The ability of monoclonal antibody (MAb 108), an immunoglobulin G (IgG)2a against the epidermal growth factor receptor (EGF-R), to interact with lung cancer cell lines was investigated. 125I-EGF bound with high affinity to non-small-cell lung cancer (NSCLC) cells, and MAb 108 inhibited specific binding of nine NSCLC cell lines in a dose-dependent manner (IC50 = 0.3-3 micrograms per ml). 125I-MAb 108 bound with high affinity (kd = 2 nM) to a single class of sites (Bmax = 70,000 per cell) using NSCLC neuroendocrine cell line NCI-H460. Specific 125I-MAb 108 binding was inhibited with high affinity by MAb 108 but not by a control antibody IgG using large-cell carcinoma cell line NCI-H1299. 125I-MAb 108 binding was not internalized at 37 degrees C using NSCLC neuroendocrine cell line NCI-H460 and adenocarcinoma cell line NCI-H23. Also, 1 microgram per ml of MAb 108 but not of a control IgG inhibited the clonal growth of NCI-H23 and squamous cell carcinoma cell line NCI-H157 in vitro. Also, MAb 108 inhibited xenograft formation of cell lines NCI-H460, NCI-H157, and NCI-H727 in nude mice in vivo. After a palpable tumor had formed using NCI-H460 cells, injection of 100 micrograms of MAb 108 (intraperitoneally three times weekly) inhibited xenograft volume in nude mice by approximately 50%. These data suggest that MAb 108 may interact with EGF receptors on lung cancer cell lines and inhibit NSCLC proliferation.
Cancer research, 1995
We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell... more We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell lung cancer cell line NCI-N417 in a previous study. In this study, the role of PACAP in the growth and signal transduction of non-small cell lung cancer cells was investigated. Northern blot analysis with a full-length human PACAP receptor cDNA probe revealed a major 7.5-kb hybridizing transcript when total RNA extracted from NCI-H838 cells was used. PACAP bound with high affinity (Kd = 1 nM) to a single class of sites (Bmax = 14,000/cell) when NCI-H838 cells were used. Specific 125I-labeled PACAP binding was inhibited with high affinity by PACAP-27 and PACAP-38, with moderate affinity by PACAP(6-38), and with low affinity by vasoactive intestinal polypeptide, PACAP(28-38), and PACAP(16-38). PACAP-27 elevated cAMP in a dose-dependent manner, and the increase in cAMP caused by PACAP was reversed by PACAP(6-38). PACAP-27, but not vasoactive intestinal polypeptide, elevated cytosolic Ca2+ ...
Biomedical Research-tokyo, 1992
The ability of VIP analogues to interact with small cell lung cancer (SCLC) cells was investigate... more The ability of VIP analogues to interact with small cell lung cancer (SCLC) cells was investigated. Specific 125 I-VIP binding to SCLC cell line NCI-H209 was inhibited with high affinity by VI, PACAP, VIPhybrid (VIPhyb) and thymosin α 1 (THNα 1 ) (IC 50 =10, 20, 700 and 10000 nM respectively) but not thymosin B 4 . 125 I-VIP bound specifically to 3 out of 5 sCLC biopsy specimens. VIP but not VIPhyb or THNα 1 elevated the cAMP levels 4-fold using cell lines NCI-H345 and H209
Journal of Clinical Oncology, 2019
TPS2645 Background: NEO-201 is a novel humanized IgG1 monoclonal antibody (mAb) generated against... more TPS2645 Background: NEO-201 is a novel humanized IgG1 monoclonal antibody (mAb) generated against the Hollinshead allogenic colorectal cancer vaccine platform. Briefly, tumor-associated antigens (TAA) derived from tumor membrane fractions pooled from colorectal cancer surgical specimens were screened for delayed-type hypersensitivity and evaluated in clinical trials. The original vaccine was used to generate monoclonal antibodies, one of which is NEO-201. In preclinical data generated in our laboratory, we have demonstrated that NEO-201 exert anti-tumor activity by natural killer (NK)-mediated antibody-dependent cytotoxicity (ADCC) against several tumor type including colorectal and pancreatic cancer models (Fantini, et al. 2018). We have identified NEO-201 antigen as a glycosylated form of CEACAM-5 and -6, which is expressed by tumor tissue but is not present in the surrounding healthy tissue (David, et al. 2018). This could result in a specific anti-tumor activity without signific...
Journal of the National Cancer Institute. Monographs, Nov 1, 2017
The Division of Cancer Treatment and Diagnosis, Office of Cancer Complementary and Alternative Me... more The Division of Cancer Treatment and Diagnosis, Office of Cancer Complementary and Alternative Medicine, at the National Cancer Institute (NCI) held a symposium on "Acupuncture for Cancer Symptom Management" on June 16 and 17, 2016. Invited speakers included 19 scientists and scholars with expertise in acupuncture and cancer research from the United States, Europe, and China. The conference reviewed the NCI's grant funding on acupuncture, analyzed the needs of cancer patients, reviewed safety issues, and assessed both the current scientific evidence and research gaps of acupuncture in oncology care. Researchers and stakeholders presented and discussed basic mechanisms of acupuncture; clinical evidence for specific symptoms; and methodological challenges such as placebo effects, novel biostatistical methods, patient-reported outcomes, and comparative effectiveness research. This paper, resulting from the conference, summarizes both the current state of the science and c...
Cancer Research
We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell... more We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell lung cancer cell line NCI-N417 in a previous study. In this study, the role of PACAP in the growth and signal transduction of non-small cell lung cancer cells was investigated. Northern blot analysis with a full-length human PACAP receptor cDNA probe revealed a major 7.5-kb hybridizing transcript when total RNA extracted from NCI-H838 cells was used. PACAP bound with high affinity (Kd = 1 nM) to a single class of sites (Bmax = 14,000/cell) when NCI-H838 cells were used. Specific 125I-labeled PACAP binding was inhibited with high affinity by PACAP-27 and PACAP-38, with moderate affinity by PACAP(6-38), and with low affinity by vasoactive intestinal polypeptide, PACAP(28-38), and PACAP(16-38). PACAP-27 elevated cAMP in a dose-dependent manner, and the increase in cAMP caused by PACAP was reversed by PACAP(6-38). PACAP-27, but not vasoactive intestinal polypeptide, elevated cytosolic Ca2+ ...
Nutrition and cancer, Jan 16, 2015
Grapes are one of the most consumed fruits in the world and are rich in polyphenols. Grape seed p... more Grapes are one of the most consumed fruits in the world and are rich in polyphenols. Grape seed proanthocyanidins (GSP) have demonstrated chemopreventive and/or chemotherapeutic effects in various cancer cell cultures and animal models. The clinical efficacy of chemotherapy is often limited by its adverse effects. Several studies show that reactive oxygen species mediate the cardiotoxicity and neurotoxicity induced by various cancer chemotherapeutic agents. This implies that concomitant administration of antioxidants may prevent these adverse effects. The review was carried out in accordance with the PRISMA guidelines. An electronic search strategy in Medline and Embase databases was conducted. Of the 41 studies reviewed, 27 studied GSP while the remainder (14) studied grape seed or skin extracts (GSE). All the studies were published in English, except 2 in Chinese. A significant percentage (34%) of the studies we reviewed assessed the effect of GSE or GSP on cardiotoxicity induced ...
Journal of cellular biochemistry. Supplement, 1996
The ability of monoclonal antibody (mAb) alpha IR-3 to interact with non-small cell lung cancer (... more The ability of monoclonal antibody (mAb) alpha IR-3 to interact with non-small cell lung cancer (NSCLC) cells was investigated. MAb alpha IR-3 inhibited specific binding of 125I-IGF-I and 125I-alpha IR-3 to a panel of 8 NSCLC cell lines with high affinity (IC50 = 200 and 50 ng/ml, respectively). 125I-alpha IR-3 bound with high affinity (Kd = 40 ng/ml) to a single class of sites (Bmax = 8,000/cell) using NCI-H838 cells. 125I-alpha IR-3 was internalized when exposed to NCI-H838 or H1299 cells at 37 degrees C but not 4 degrees C. alpha IR-3 immunoprecipitated major 90 and 130 kD proteins. IGF-I stimulated and alpha IR-3 inhibited the clonal growth of NCI-H1299 cells. alpha IR-3 slowed the growth of NCI-H157 and H838 xenografts in nude mice. In a biodistribution study 125I-alpha IR-3 was preferentially localized to the tumor as opposed to other organs. These data suggest that IGF-I may be a regulatory agent in NSCLC.
Cancer research, 1993
The effect of thymosin alpha 1 (THN alpha 1) and its NH2-terminal fragment (THN1-14) and COOH-ter... more The effect of thymosin alpha 1 (THN alpha 1) and its NH2-terminal fragment (THN1-14) and COOH-terminal fragment (THN15-28) on non-small cell lung cancer (NSCLC) growth was evaluated. Using an anti-THN alpha 1 antibody, receptors were identified on NSCLC cells that were pretreated with 10(-6) M THN alpha 1. [3H]Arachidonic acid was readily taken up by NSCLC cells and THN alpha 1 significantly increased the rate of arachidonic acid release. THN1-15 slightly stimulated but THN15-28 and THN beta 4 did not alter arachidonic acid release from NCI-H1299 cells. In clonogenic growth assays in vitro, THN alpha 1 (10(-6) M) significantly decreased NSCLC colony number whereas THN1-14, THN15-28, and THN beta 4 were less potent. Using growth assays in vivo, THN alpha 1 (10 micrograms s.c./day) but not THN1-14, THN15-28, or THN beta 4 inhibited significantly NSCLC xenograft formation in nude mice. These data suggest that biologically active THN alpha 1 receptors are present on NSCLC cells and that...
Peptides, 1994
The effects of corticotropin-releasing factor (CRF) on human lung cancer cell lines was investiga... more The effects of corticotropin-releasing factor (CRF) on human lung cancer cell lines was investigated. Corticotropin-releasing factor increased the cAMP levels in a dose-dependent manner; CRF (100 nM) elevated the cAMP levels approximately eleven-fold using NCI-H345 cells and increased the gastrin-releasing peptide (GRP) secretion rate by approximately 70%. Similarly, sauvagine, a structural analogue of CRF, elevated the cAMP levels with a half-maximal effective dose (ED50) of 20 nM. The increase in cAMP caused by CRF and sauvagine was reversed by alpha-helical CRF(9-41). Corticotropin-releasing factor had no effect on cytosolic calcium but stimulated [3H]arachidonic acid release from NCI-H1299 cells with an ED50 of 30 nM. The increase in [3H]arachidonic acid release caused by 100 nM CRF was significantly reversed by 1 or 10 microM alpha-helical CRF(9-41). Also, CRF stimulated the clonal growth of NCI-H345 and H720 cells and the growth increase caused by CRF was reversed by alpha-helical CRF(9-41). These data suggest that CRF may be a regulatory peptide in lung cancer.
Peptides, 1995
The effects of neuromedin B (NMB) on C6 glioma cells were investigated. NMB bound with high affin... more The effects of neuromedin B (NMB) on C6 glioma cells were investigated. NMB bound with high affinity (IC50 = 1 nM) to C6 cells whereas BN and GRP were less potent (IC50 = 40 and 100 nM). NMB (1 nM) elevated cytosolic Ca2+ in individual C6 cells and the increase in cytosolic Ca2+ was reversed by 1 microM [D-Arg1, D-Pro2,D-Trp7.9,Leu11]substance P [APTTL]SP, a broad spectrum antagonist. NMB stimulated [3H]arachidonic acid release from C6 cells and the increase in [3H]arachidonic acid release was reversed [APTTL]SP. NMB increased transiently c-fos gene expression in C6 cells. NMB increased the number of C6 colonies in soft agar and the increase in growth caused by NMB was reversed by [APTTL]SP. These data suggest that NMB receptors may regulate the proliferation of C6 cells.
Lung Cancer, 2001
The effects of prostaglandin E 2 (PGE 2) and vasoactive intestinal peptide (VIP) on vascular endo... more The effects of prostaglandin E 2 (PGE 2) and vasoactive intestinal peptide (VIP) on vascular endothelial cell growth factor (VEGF) mRNAs were investigated using lung cancer cells. By RT-PCR, VEGF 121 , VEGF 165 , and VEGF 189 , but not VEGF 206 isoforms were detected in all lung cancer cell lines and biopsy specimens examined. By Northern blot, VEGF mRNA was detected in all small cell lung cancer (SCLC) and non-SCLC (NSCLC) cell lines examined. PGE 2 , VIP and forskolin caused increased VEGF expression in a time-and concentration-dependent manner using NSCLC cell line NCI-H157. Approximately 1 mM PGE 2 , 0.1 mM VIP and 50 mM forskolin caused cAMP elevation, 64-, 33-and 128-fold, respectively, using NCI-H157 cells after 5 min. The increase in cAMP caused by PGE 2 and VIP was reversed by somatostatin (SST). Also 1 mM PGE 2 , 0.1 mM VIP and 50 mM forskolin increased the VEGF mRNA 2.0-, 1.5-and 2.3-fold, respectively, after 4 h. The increase in VEGF mRNA caused by PGE 2 , VIP and forskolin was inhibited by H-89, a protein kinase A inhibitor. A VIP receptor antagonist, VIPhybrid, inhibited the increase in cAMP and VEGF mRNA caused by VIP. By ELISA, VEGF was detected in the conditioned media exposed to the lung cancer cell lines. These results suggest that VEGF synthesis in and secretion from lung cancer cells can be regulated by agents, which cause adenylyl cyclase activation.
Journal of Molecular Neuroscience, 2001
The most prevalent lung cancer, non-small cell lung cancer (NSCLC) has receptors for vasoactive i... more The most prevalent lung cancer, non-small cell lung cancer (NSCLC) has receptors for vasoactive intestinal peptide (VIP). Here the effects of a VIP antagonist (VIPhyb) on NSCLC growth were investigated. In vivo, when VIPhyb (10 ,ug, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by-40%. In vitro, VIP (100 nM) stimulated colony formation-2-fold, whereas 1 ,uM VIPhyb inhibited colony formation by-50% when adenocarcinoma cel line NCI-H838 was used. The attenuation of tumor proliferation is receptor mediated, as VIPhyb inhibited specific 12sI-labeled VIP binding to cell lines NCI-H157 and NCI-H838 with an IC5s of 0.7 ,M. VIP (10 nM) increased the cAMP levels 5-fold when ceUl line NCI-H838 was used, and 10 ,uM VIPhyb inhibited the increase in cAMP caused by VIP. Northern blot analysis and radioimmunoassays have shown VIP mRNA and VIP-like immunoreactivity in NSCLC cells. These data suggest that VIP may be a regulatory peptide in NSCLC and that VIPhyb is a VIP receptor antagonist that inhibits proliferation.
Journal of Cellular Biochemistry, 1996
The ability of monoclonal antibody (mAb) alR-3 to interact with non-small cell lung cancer (NSCLC... more The ability of monoclonal antibody (mAb) alR-3 to interact with non-small cell lung cancer (NSCLC) cells was investigated. MAb alR-3 inhibited specific binding of 1251-IGF-I and 1251-alR-3 to a panel of 8 NSCLC cell lines with high affinity (IC50 = 200 and 50 ng/ml, respectively). 1251-alR-3 bound with high affinity (Kd = 40 ng/ml) to a single class of sites (Bmax = 8,00O/cell) using NCLH838 cells. 1251-alR-3 was internalized when exposed to N O H 8 3 8 or H I 2 9 9 cells at 37°C but not 4°C. alR-3 irnmunoprecipitated major 9 0 and 130 kD proteins. IGF-I stimulated and alR-3 inhibited the clonal growth of NCI-HI299 cells. aIR-3 slowed the growth of NCI-HI57 and H838 xenografts in nude mice. In a biodistribution study 1251-alR-3 was preferentially localized to the tumor as opposed to other organs. These data suggest that IGF-I may be a regulatory agent in NSCLC.
Journal of Cellular Biochemistry, 1996
Previously, GRP receptors were characterized in small cell lung cancer cells and here non-small c... more Previously, GRP receptors were characterized in small cell lung cancer cells and here non-small cell lung cancer (NSCLC) cells were investigated: (1251-Tyr4) bombesin (BN) or lZ51-GRP bound with high affinity to NCLH720 (lung carcinoid) and NCI-HI 299 (large cell carcinoma) cells. Binding was specific, time dependent, and saturable. Specific (1251-Tyr4)BN binding to NCI-HI299 cells was inhibited with high affinity by GRP, BN, CRP'"27, (D-Phe6)BNG13methyl ester, moderate affinity by NMB, and low affinity by GRP1-I6. BN (10 nM) transiently elevated cytosolic calcium in a dose dependent manner. BN caused translocation of protein kinase C from the cytosol to the membrane and the translocation caused by BN was reversed by (D-Phe6)BN613methylester. BN stimulated arachidonic acid release and the increase caused by BN was reversed by (D-Phe6)BNG13methylester. Using a clonogenic assay, BN stimulated the growth of NCLH720 cells, and the number of colonies was reduced using (D-Phe6)BNG13methylester. These data suggest that GRP receptors that are present in lung carcinoid and NSCLC cells may regulate proliferation.
Integrative Cancer Therapies, 2013
Objectives. The National Cancer Institute (NCI) Best Case Series (BCS) Program provides an indepe... more Objectives. The National Cancer Institute (NCI) Best Case Series (BCS) Program provides an independent review of medical records, imaging, and pathology of cancer patients treated with unconventional therapies. The goal of the NCI BCS Program is to identify preliminary evidence of tumor regression and assess whether there is sufficient evidence to move forward with NCI-initiated research. The objective was to review case reports submitted by 4 practitioners from India who used ayurvedic and homeopathic therapies to treat cancer. Design. Retrospective review of case reports of 4 practitioners from India who used ayurvedic and homeopathic therapies to treat cancer. Results. A total of 68 cases were submitted to the NCI BCS Program. Fifty-one percent of the cases represented homeopathy and 49% ayurveda. Of the 68 cases, 32 (47%) of the cases were collectively designated as “persuasive” (P) or “supportive”(S), and 36 (53%) as “not evaluable.” Forty-one (60%) patients did not have any pr...
Cancer Letters, 2000
The effects of thymosin (THN) α1 were investigated using the urethane injection carcinogenesis A/... more The effects of thymosin (THN) α1 were investigated using the urethane injection carcinogenesis A/J mouse model. Lung adenomas were observed 2.5, 3, and 4 months after urethane injection (400 mg/kg i.p.) into female A/J mice. Daily administration of THNα1 (0.4 mg/kg, s.c.) reduced lung adenoma multiplicity significantly, by approximately 45, 40, and 17%, respectively, 2.5, 3, and 4 months after urethane injection. Animals treated with THNα1 had a significantly greater white cell density than control A/J mice. Endogenous THNα1-like peptides were detected in the mouse lung. By radioimmunoassay and by Western blot, prothymosin α was detected in the mouse lung. By immunocytochemistry, THNα1-like peptides were detected in all lung compartments including the bronchus, adenoma, bronchioles, and alveoli. These results indicate that exogenous THNα1 prevents lung carcinogenesis in A/J mice.
PubMed, Nov 1, 1993
The effect of thymosin alpha 1 (THN alpha 1) and its NH2-terminal fragment (THN1-14) and COOH-ter... more The effect of thymosin alpha 1 (THN alpha 1) and its NH2-terminal fragment (THN1-14) and COOH-terminal fragment (THN15-28) on non-small cell lung cancer (NSCLC) growth was evaluated. Using an anti-THN alpha 1 antibody, receptors were identified on NSCLC cells that were pretreated with 10(-6) M THN alpha 1. [3H]Arachidonic acid was readily taken up by NSCLC cells and THN alpha 1 significantly increased the rate of arachidonic acid release. THN1-15 slightly stimulated but THN15-28 and THN beta 4 did not alter arachidonic acid release from NCI-H1299 cells. In clonogenic growth assays in vitro, THN alpha 1 (10(-6) M) significantly decreased NSCLC colony number whereas THN1-14, THN15-28, and THN beta 4 were less potent. Using growth assays in vivo, THN alpha 1 (10 micrograms s.c./day) but not THN1-14, THN15-28, or THN beta 4 inhibited significantly NSCLC xenograft formation in nude mice. These data suggest that biologically active THN alpha 1 receptors are present on NSCLC cells and that native THN alpha 1 inhibits the growth of human NSCLC.
Annals of the New York Academy of Sciences, Jan 25, 2006
VIP/PACAP are autocrine growth factors for lung cancer. VIP and/or PACAP mRNA is present in most ... more VIP/PACAP are autocrine growth factors for lung cancer. VIP and/or PACAP mRNA is present in most lung cancer cell lines examined. Although mRNA for VPAC2-R is not common, VPAC1-R and PAC1-R mRNA is present in many lung cancer cell lines. 125I-VIP binds with high affinity to lung cancer cells and specific 125I-VIP binding is inhibited with high affinity by (Lys15, Arg16, Leu27)VIP1-7 GRF8-27, the VPAC1-R specific agonist, but not by Ro25-1553(18), the VPAC2-R specific agonist. VIP elevates cAMP and increases c-fos gene expression. The increase in cAMP and c-fos mRNA caused by VIP is inhibited by SN(VH). (SH)VH inhibited the proliferation of NCIH1299 cells in the MTT assay, which is based on cytotoxicity. In a recent cell line screen, (SN)VH inhibited the growth of 51 of 56 cancer cell lines including leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, breast cancer, and prostate cancer (T. Moody, unpublished). It remains to be determined if (SN)VH will be useful for treatment of a wide variety of cancers.
PubMed, 1992
The ability of monoclonal antibody (MAb 108), an immunoglobulin G (IgG)2a against the epidermal g... more The ability of monoclonal antibody (MAb 108), an immunoglobulin G (IgG)2a against the epidermal growth factor receptor (EGF-R), to interact with lung cancer cell lines was investigated. 125I-EGF bound with high affinity to non-small-cell lung cancer (NSCLC) cells, and MAb 108 inhibited specific binding of nine NSCLC cell lines in a dose-dependent manner (IC50 = 0.3-3 micrograms per ml). 125I-MAb 108 bound with high affinity (kd = 2 nM) to a single class of sites (Bmax = 70,000 per cell) using NSCLC neuroendocrine cell line NCI-H460. Specific 125I-MAb 108 binding was inhibited with high affinity by MAb 108 but not by a control antibody IgG using large-cell carcinoma cell line NCI-H1299. 125I-MAb 108 binding was not internalized at 37 degrees C using NSCLC neuroendocrine cell line NCI-H460 and adenocarcinoma cell line NCI-H23. Also, 1 microgram per ml of MAb 108 but not of a control IgG inhibited the clonal growth of NCI-H23 and squamous cell carcinoma cell line NCI-H157 in vitro. Also, MAb 108 inhibited xenograft formation of cell lines NCI-H460, NCI-H157, and NCI-H727 in nude mice in vivo. After a palpable tumor had formed using NCI-H460 cells, injection of 100 micrograms of MAb 108 (intraperitoneally three times weekly) inhibited xenograft volume in nude mice by approximately 50%. These data suggest that MAb 108 may interact with EGF receptors on lung cancer cell lines and inhibit NSCLC proliferation.
Cancer research, 1995
We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell... more We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell lung cancer cell line NCI-N417 in a previous study. In this study, the role of PACAP in the growth and signal transduction of non-small cell lung cancer cells was investigated. Northern blot analysis with a full-length human PACAP receptor cDNA probe revealed a major 7.5-kb hybridizing transcript when total RNA extracted from NCI-H838 cells was used. PACAP bound with high affinity (Kd = 1 nM) to a single class of sites (Bmax = 14,000/cell) when NCI-H838 cells were used. Specific 125I-labeled PACAP binding was inhibited with high affinity by PACAP-27 and PACAP-38, with moderate affinity by PACAP(6-38), and with low affinity by vasoactive intestinal polypeptide, PACAP(28-38), and PACAP(16-38). PACAP-27 elevated cAMP in a dose-dependent manner, and the increase in cAMP caused by PACAP was reversed by PACAP(6-38). PACAP-27, but not vasoactive intestinal polypeptide, elevated cytosolic Ca2+ ...
Biomedical Research-tokyo, 1992
The ability of VIP analogues to interact with small cell lung cancer (SCLC) cells was investigate... more The ability of VIP analogues to interact with small cell lung cancer (SCLC) cells was investigated. Specific 125 I-VIP binding to SCLC cell line NCI-H209 was inhibited with high affinity by VI, PACAP, VIPhybrid (VIPhyb) and thymosin α 1 (THNα 1 ) (IC 50 =10, 20, 700 and 10000 nM respectively) but not thymosin B 4 . 125 I-VIP bound specifically to 3 out of 5 sCLC biopsy specimens. VIP but not VIPhyb or THNα 1 elevated the cAMP levels 4-fold using cell lines NCI-H345 and H209
Journal of Clinical Oncology, 2019
TPS2645 Background: NEO-201 is a novel humanized IgG1 monoclonal antibody (mAb) generated against... more TPS2645 Background: NEO-201 is a novel humanized IgG1 monoclonal antibody (mAb) generated against the Hollinshead allogenic colorectal cancer vaccine platform. Briefly, tumor-associated antigens (TAA) derived from tumor membrane fractions pooled from colorectal cancer surgical specimens were screened for delayed-type hypersensitivity and evaluated in clinical trials. The original vaccine was used to generate monoclonal antibodies, one of which is NEO-201. In preclinical data generated in our laboratory, we have demonstrated that NEO-201 exert anti-tumor activity by natural killer (NK)-mediated antibody-dependent cytotoxicity (ADCC) against several tumor type including colorectal and pancreatic cancer models (Fantini, et al. 2018). We have identified NEO-201 antigen as a glycosylated form of CEACAM-5 and -6, which is expressed by tumor tissue but is not present in the surrounding healthy tissue (David, et al. 2018). This could result in a specific anti-tumor activity without signific...
Journal of the National Cancer Institute. Monographs, Nov 1, 2017
The Division of Cancer Treatment and Diagnosis, Office of Cancer Complementary and Alternative Me... more The Division of Cancer Treatment and Diagnosis, Office of Cancer Complementary and Alternative Medicine, at the National Cancer Institute (NCI) held a symposium on "Acupuncture for Cancer Symptom Management" on June 16 and 17, 2016. Invited speakers included 19 scientists and scholars with expertise in acupuncture and cancer research from the United States, Europe, and China. The conference reviewed the NCI's grant funding on acupuncture, analyzed the needs of cancer patients, reviewed safety issues, and assessed both the current scientific evidence and research gaps of acupuncture in oncology care. Researchers and stakeholders presented and discussed basic mechanisms of acupuncture; clinical evidence for specific symptoms; and methodological challenges such as placebo effects, novel biostatistical methods, patient-reported outcomes, and comparative effectiveness research. This paper, resulting from the conference, summarizes both the current state of the science and c...
Cancer Research
We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell... more We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell lung cancer cell line NCI-N417 in a previous study. In this study, the role of PACAP in the growth and signal transduction of non-small cell lung cancer cells was investigated. Northern blot analysis with a full-length human PACAP receptor cDNA probe revealed a major 7.5-kb hybridizing transcript when total RNA extracted from NCI-H838 cells was used. PACAP bound with high affinity (Kd = 1 nM) to a single class of sites (Bmax = 14,000/cell) when NCI-H838 cells were used. Specific 125I-labeled PACAP binding was inhibited with high affinity by PACAP-27 and PACAP-38, with moderate affinity by PACAP(6-38), and with low affinity by vasoactive intestinal polypeptide, PACAP(28-38), and PACAP(16-38). PACAP-27 elevated cAMP in a dose-dependent manner, and the increase in cAMP caused by PACAP was reversed by PACAP(6-38). PACAP-27, but not vasoactive intestinal polypeptide, elevated cytosolic Ca2+ ...
Nutrition and cancer, Jan 16, 2015
Grapes are one of the most consumed fruits in the world and are rich in polyphenols. Grape seed p... more Grapes are one of the most consumed fruits in the world and are rich in polyphenols. Grape seed proanthocyanidins (GSP) have demonstrated chemopreventive and/or chemotherapeutic effects in various cancer cell cultures and animal models. The clinical efficacy of chemotherapy is often limited by its adverse effects. Several studies show that reactive oxygen species mediate the cardiotoxicity and neurotoxicity induced by various cancer chemotherapeutic agents. This implies that concomitant administration of antioxidants may prevent these adverse effects. The review was carried out in accordance with the PRISMA guidelines. An electronic search strategy in Medline and Embase databases was conducted. Of the 41 studies reviewed, 27 studied GSP while the remainder (14) studied grape seed or skin extracts (GSE). All the studies were published in English, except 2 in Chinese. A significant percentage (34%) of the studies we reviewed assessed the effect of GSE or GSP on cardiotoxicity induced ...
Journal of cellular biochemistry. Supplement, 1996
The ability of monoclonal antibody (mAb) alpha IR-3 to interact with non-small cell lung cancer (... more The ability of monoclonal antibody (mAb) alpha IR-3 to interact with non-small cell lung cancer (NSCLC) cells was investigated. MAb alpha IR-3 inhibited specific binding of 125I-IGF-I and 125I-alpha IR-3 to a panel of 8 NSCLC cell lines with high affinity (IC50 = 200 and 50 ng/ml, respectively). 125I-alpha IR-3 bound with high affinity (Kd = 40 ng/ml) to a single class of sites (Bmax = 8,000/cell) using NCI-H838 cells. 125I-alpha IR-3 was internalized when exposed to NCI-H838 or H1299 cells at 37 degrees C but not 4 degrees C. alpha IR-3 immunoprecipitated major 90 and 130 kD proteins. IGF-I stimulated and alpha IR-3 inhibited the clonal growth of NCI-H1299 cells. alpha IR-3 slowed the growth of NCI-H157 and H838 xenografts in nude mice. In a biodistribution study 125I-alpha IR-3 was preferentially localized to the tumor as opposed to other organs. These data suggest that IGF-I may be a regulatory agent in NSCLC.
Cancer research, 1993
The effect of thymosin alpha 1 (THN alpha 1) and its NH2-terminal fragment (THN1-14) and COOH-ter... more The effect of thymosin alpha 1 (THN alpha 1) and its NH2-terminal fragment (THN1-14) and COOH-terminal fragment (THN15-28) on non-small cell lung cancer (NSCLC) growth was evaluated. Using an anti-THN alpha 1 antibody, receptors were identified on NSCLC cells that were pretreated with 10(-6) M THN alpha 1. [3H]Arachidonic acid was readily taken up by NSCLC cells and THN alpha 1 significantly increased the rate of arachidonic acid release. THN1-15 slightly stimulated but THN15-28 and THN beta 4 did not alter arachidonic acid release from NCI-H1299 cells. In clonogenic growth assays in vitro, THN alpha 1 (10(-6) M) significantly decreased NSCLC colony number whereas THN1-14, THN15-28, and THN beta 4 were less potent. Using growth assays in vivo, THN alpha 1 (10 micrograms s.c./day) but not THN1-14, THN15-28, or THN beta 4 inhibited significantly NSCLC xenograft formation in nude mice. These data suggest that biologically active THN alpha 1 receptors are present on NSCLC cells and that...
Peptides, 1994
The effects of corticotropin-releasing factor (CRF) on human lung cancer cell lines was investiga... more The effects of corticotropin-releasing factor (CRF) on human lung cancer cell lines was investigated. Corticotropin-releasing factor increased the cAMP levels in a dose-dependent manner; CRF (100 nM) elevated the cAMP levels approximately eleven-fold using NCI-H345 cells and increased the gastrin-releasing peptide (GRP) secretion rate by approximately 70%. Similarly, sauvagine, a structural analogue of CRF, elevated the cAMP levels with a half-maximal effective dose (ED50) of 20 nM. The increase in cAMP caused by CRF and sauvagine was reversed by alpha-helical CRF(9-41). Corticotropin-releasing factor had no effect on cytosolic calcium but stimulated [3H]arachidonic acid release from NCI-H1299 cells with an ED50 of 30 nM. The increase in [3H]arachidonic acid release caused by 100 nM CRF was significantly reversed by 1 or 10 microM alpha-helical CRF(9-41). Also, CRF stimulated the clonal growth of NCI-H345 and H720 cells and the growth increase caused by CRF was reversed by alpha-helical CRF(9-41). These data suggest that CRF may be a regulatory peptide in lung cancer.
Peptides, 1995
The effects of neuromedin B (NMB) on C6 glioma cells were investigated. NMB bound with high affin... more The effects of neuromedin B (NMB) on C6 glioma cells were investigated. NMB bound with high affinity (IC50 = 1 nM) to C6 cells whereas BN and GRP were less potent (IC50 = 40 and 100 nM). NMB (1 nM) elevated cytosolic Ca2+ in individual C6 cells and the increase in cytosolic Ca2+ was reversed by 1 microM [D-Arg1, D-Pro2,D-Trp7.9,Leu11]substance P [APTTL]SP, a broad spectrum antagonist. NMB stimulated [3H]arachidonic acid release from C6 cells and the increase in [3H]arachidonic acid release was reversed [APTTL]SP. NMB increased transiently c-fos gene expression in C6 cells. NMB increased the number of C6 colonies in soft agar and the increase in growth caused by NMB was reversed by [APTTL]SP. These data suggest that NMB receptors may regulate the proliferation of C6 cells.
Lung Cancer, 2001
The effects of prostaglandin E 2 (PGE 2) and vasoactive intestinal peptide (VIP) on vascular endo... more The effects of prostaglandin E 2 (PGE 2) and vasoactive intestinal peptide (VIP) on vascular endothelial cell growth factor (VEGF) mRNAs were investigated using lung cancer cells. By RT-PCR, VEGF 121 , VEGF 165 , and VEGF 189 , but not VEGF 206 isoforms were detected in all lung cancer cell lines and biopsy specimens examined. By Northern blot, VEGF mRNA was detected in all small cell lung cancer (SCLC) and non-SCLC (NSCLC) cell lines examined. PGE 2 , VIP and forskolin caused increased VEGF expression in a time-and concentration-dependent manner using NSCLC cell line NCI-H157. Approximately 1 mM PGE 2 , 0.1 mM VIP and 50 mM forskolin caused cAMP elevation, 64-, 33-and 128-fold, respectively, using NCI-H157 cells after 5 min. The increase in cAMP caused by PGE 2 and VIP was reversed by somatostatin (SST). Also 1 mM PGE 2 , 0.1 mM VIP and 50 mM forskolin increased the VEGF mRNA 2.0-, 1.5-and 2.3-fold, respectively, after 4 h. The increase in VEGF mRNA caused by PGE 2 , VIP and forskolin was inhibited by H-89, a protein kinase A inhibitor. A VIP receptor antagonist, VIPhybrid, inhibited the increase in cAMP and VEGF mRNA caused by VIP. By ELISA, VEGF was detected in the conditioned media exposed to the lung cancer cell lines. These results suggest that VEGF synthesis in and secretion from lung cancer cells can be regulated by agents, which cause adenylyl cyclase activation.
Journal of Molecular Neuroscience, 2001
The most prevalent lung cancer, non-small cell lung cancer (NSCLC) has receptors for vasoactive i... more The most prevalent lung cancer, non-small cell lung cancer (NSCLC) has receptors for vasoactive intestinal peptide (VIP). Here the effects of a VIP antagonist (VIPhyb) on NSCLC growth were investigated. In vivo, when VIPhyb (10 ,ug, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by-40%. In vitro, VIP (100 nM) stimulated colony formation-2-fold, whereas 1 ,uM VIPhyb inhibited colony formation by-50% when adenocarcinoma cel line NCI-H838 was used. The attenuation of tumor proliferation is receptor mediated, as VIPhyb inhibited specific 12sI-labeled VIP binding to cell lines NCI-H157 and NCI-H838 with an IC5s of 0.7 ,M. VIP (10 nM) increased the cAMP levels 5-fold when ceUl line NCI-H838 was used, and 10 ,uM VIPhyb inhibited the increase in cAMP caused by VIP. Northern blot analysis and radioimmunoassays have shown VIP mRNA and VIP-like immunoreactivity in NSCLC cells. These data suggest that VIP may be a regulatory peptide in NSCLC and that VIPhyb is a VIP receptor antagonist that inhibits proliferation.
Journal of Cellular Biochemistry, 1996
The ability of monoclonal antibody (mAb) alR-3 to interact with non-small cell lung cancer (NSCLC... more The ability of monoclonal antibody (mAb) alR-3 to interact with non-small cell lung cancer (NSCLC) cells was investigated. MAb alR-3 inhibited specific binding of 1251-IGF-I and 1251-alR-3 to a panel of 8 NSCLC cell lines with high affinity (IC50 = 200 and 50 ng/ml, respectively). 1251-alR-3 bound with high affinity (Kd = 40 ng/ml) to a single class of sites (Bmax = 8,00O/cell) using NCLH838 cells. 1251-alR-3 was internalized when exposed to N O H 8 3 8 or H I 2 9 9 cells at 37°C but not 4°C. alR-3 irnmunoprecipitated major 9 0 and 130 kD proteins. IGF-I stimulated and alR-3 inhibited the clonal growth of NCI-HI299 cells. aIR-3 slowed the growth of NCI-HI57 and H838 xenografts in nude mice. In a biodistribution study 1251-alR-3 was preferentially localized to the tumor as opposed to other organs. These data suggest that IGF-I may be a regulatory agent in NSCLC.
Journal of Cellular Biochemistry, 1996
Previously, GRP receptors were characterized in small cell lung cancer cells and here non-small c... more Previously, GRP receptors were characterized in small cell lung cancer cells and here non-small cell lung cancer (NSCLC) cells were investigated: (1251-Tyr4) bombesin (BN) or lZ51-GRP bound with high affinity to NCLH720 (lung carcinoid) and NCI-HI 299 (large cell carcinoma) cells. Binding was specific, time dependent, and saturable. Specific (1251-Tyr4)BN binding to NCI-HI299 cells was inhibited with high affinity by GRP, BN, CRP'"27, (D-Phe6)BNG13methyl ester, moderate affinity by NMB, and low affinity by GRP1-I6. BN (10 nM) transiently elevated cytosolic calcium in a dose dependent manner. BN caused translocation of protein kinase C from the cytosol to the membrane and the translocation caused by BN was reversed by (D-Phe6)BN613methylester. BN stimulated arachidonic acid release and the increase caused by BN was reversed by (D-Phe6)BNG13methylester. Using a clonogenic assay, BN stimulated the growth of NCLH720 cells, and the number of colonies was reduced using (D-Phe6)BNG13methylester. These data suggest that GRP receptors that are present in lung carcinoid and NSCLC cells may regulate proliferation.
Integrative Cancer Therapies, 2013
Objectives. The National Cancer Institute (NCI) Best Case Series (BCS) Program provides an indepe... more Objectives. The National Cancer Institute (NCI) Best Case Series (BCS) Program provides an independent review of medical records, imaging, and pathology of cancer patients treated with unconventional therapies. The goal of the NCI BCS Program is to identify preliminary evidence of tumor regression and assess whether there is sufficient evidence to move forward with NCI-initiated research. The objective was to review case reports submitted by 4 practitioners from India who used ayurvedic and homeopathic therapies to treat cancer. Design. Retrospective review of case reports of 4 practitioners from India who used ayurvedic and homeopathic therapies to treat cancer. Results. A total of 68 cases were submitted to the NCI BCS Program. Fifty-one percent of the cases represented homeopathy and 49% ayurveda. Of the 68 cases, 32 (47%) of the cases were collectively designated as “persuasive” (P) or “supportive”(S), and 36 (53%) as “not evaluable.” Forty-one (60%) patients did not have any pr...
Cancer Letters, 2000
The effects of thymosin (THN) α1 were investigated using the urethane injection carcinogenesis A/... more The effects of thymosin (THN) α1 were investigated using the urethane injection carcinogenesis A/J mouse model. Lung adenomas were observed 2.5, 3, and 4 months after urethane injection (400 mg/kg i.p.) into female A/J mice. Daily administration of THNα1 (0.4 mg/kg, s.c.) reduced lung adenoma multiplicity significantly, by approximately 45, 40, and 17%, respectively, 2.5, 3, and 4 months after urethane injection. Animals treated with THNα1 had a significantly greater white cell density than control A/J mice. Endogenous THNα1-like peptides were detected in the mouse lung. By radioimmunoassay and by Western blot, prothymosin α was detected in the mouse lung. By immunocytochemistry, THNα1-like peptides were detected in all lung compartments including the bronchus, adenoma, bronchioles, and alveoli. These results indicate that exogenous THNα1 prevents lung carcinogenesis in A/J mice.