Improved in vivo antitumor effect of a daunorubicin - GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice

Summary Compared to classical chemotherapy, peptide-based drug targeting is a promising therapeutic approach for cancer, which can provide increased selectivity and decreased side effects to anticancer drugs. Among various homing devices, gonadotropin-releasing hormone-III (GnRH-III) peptide represents a suitable targeting moiety, in particular in the treatment of hormone independent tumors that highly express GnRH receptors (e.g. colon carcinoma). We have previously shown that GnRH-III[4Lys(Ac),8Lys(Dau = Aoa)] bioconjugate, in which daunorubicin was attached via oxime linkage to the 8Lys of a GnRH-III derivative, exerted significant in vivo antitumor effect on subcutaneously developed HT-29 colon tumor. In contrast, results of the study reported here indicated that this compound was not active on an orthotopically developed tumor. However, if Lys in position 4 was acylated with butyric acid instead of acetic acid, the resulting bioconjugate GnRH-III[4Lys(Bu),8Lys(Dau = Aoa)] had significant tumor growth inhibitory effect. Furthermore, it prevented tumor neovascularization, without detectable side effects. Nevertheless, the development of metastases could not be inhibited by the bioconjugate; therefore, its application in combination with a metastasis preventive agent might be necessary in order to achieve complete tumor remission. In spite of this result, the treatment with GnRH-III[4Lys(Bu),8Lys(Dau = Aoa)] bioconjugate proved to have...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

Related Links:

In this study, we explored the mechanism of 5-FU resistance by bioinformatics analysis of the NCBI public dataset series GSE81005. Fifteen hub genes were screened out of 582 different expressed genes. Modules of the hub genes in protein-protein interaction networks gathered to TOP2α showed a decrease in HCT-8 cells but an increase in 5-FU-resistant HCT-8/5-FU cells with 5-FU exposure. Downregulation of TOP2α with siRNA or miR-494 transfection resulted in an increase of cytotoxicity and decrease of cell colonies to 5-FU for HCT-8/5-FU cells. Moreover, we found that an ethanol extract of Spica Prunellae (E...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
ConclusionTo optimize targeting and visualization of the surgical field in right pelvic sidewall/paracolic gutter, robotic arms can be placed in a straight line from above the pubic symphysis extending to the left subcostal line and between the midline vertical and midclavicular lines. Robotic tumor debulking should be considered in selected patients with recurrent ovarian cancer who present with oligo-metastatic disease, in the absence of carcinomatosis.
Source: Journal of Minimally Invasive Gynecology - Category: OBGYN Source Type: research
We reported a case of a 66-year-old man after surgery, chemotherapy, and radiation therapy for colon cancer. Two months after these therapies, the patient complained of nonproductive cough for 1 week. Diagnoses: 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scanning revealed increased FDG uptake along the thickened bronchovascular bundles, in bilaterally scattered ground-glass opacities and in mediastinal lymphadenopathy. The transbronchial biopsy and pathological study confirmed the diagnosis of PLC. Interventions: Antineoplastic treatment (cetuximab) were administered afte...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
ConclusionsDevelopment of PD-1 B-cell vaccine was successful, showing no evidence of toxicity or autoimmunity in mice, rabbits and beagle dogs. The combination vaccines could provide improved outcomes in early stage disease sparing patients the toxicity of chemotherapy. A phase 1 clinical trial with the PD-1 vaccine is under planning.Legal entity responsible for the studyThe authors.FundingNIH; Imugene.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Abstract A 60-year-old Caucasian male was diagnosed with lung adenocarcinoma and multiple metastases to the bone, spleen, and brain. He underwent radiotherapy for the brain and lumbar spine metastases, plus chemotherapy (cisplatin and pemetrexed). The chemotherapy was discontinued due to vomiting and hyponatremia, and nivolumab was then administered. Eight months later, 18F-fluorodeoxyglucose positron emission tomography showed tracer uptake in the colon. Colonoscopy revealed a reddish multinodular polyp in the sigmoid colon. The polyp showed irregular microvessels. No colonic mucosal surface structures were obser...
Source: Acta Med Okayama - Category: Universities & Medical Training Authors: Tags: Acta Med Okayama Source Type: research
CONCLUSION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated low-volume colorectal peritoneal metastases are not safe and effective, with low morbidity. It offers selected patients a highly favorable overall and relapse-free survival. See Video Abstract at http://links.lww.com/DCR/B2. EVOLUCIÓN DE LA CIRUGÍA CITORREDUCTIVA Y QUIMIOTERAPIA INTRAPERITONEAL HIPERTÉRMICA (HIPEC) PARA METÁSTASIS PERITONEALES COLORRECTALES: EXPERIENCIA INSTITUCIONAL DE 8 AÑOS ANTECEDENTES: El cáncer colorrectal es la segunda causa de mortalidad relacionada con el c&a...
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original contributions: Colorectal Cancer Source Type: research
We describe two patients with advanced non ‐small‐cell lung cancer (NSCLC), including one in whom the definitive diagnosis of pulmonary pleomorphic carcinoma (PPC) was made by histopathology of the resected tumour and another in whom the diagnosis of “favor adenocarcinoma containing sarcomatoid components” was made by tissue biopsy. Both were resistant to first line platinum‐based chemotherapy, but responded dramatically to second line nivolumab therapy. We present two cases of pulmonary pleomorphic carcinoma (PPC) treated with Nivolumab. A 57 ‐year‐old man presented with a 3.5‐cm mass in the left l...
Source: Respirology Case Reports - Category: Respiratory Medicine Authors: Tags: Case Report Source Type: research
Publication date: October 2019Source: Biomedicine &Pharmacotherapy, Volume 118Author(s): Maria Condello, Evelin Pellegrini, Enrico Pierluigi Spugnini, Alfonso Baldi, Bruno Amadio, Bruno Vincenzi, Giovanni Occhionero, Sebastiano Delfine, Franco Mastrodonato, Stefania MeschiniAbstractIn 2018 there were over 1.8 million new cases worldwide of colorectal cancer and relapses after clinical treatments. Many studies ascribe the risk of the appearance of this cancer to the Western life style : a sedentary life, obesity, and low -fiber, high -fat diets can promote the onset of disease. Several studies have shown supplement phyt...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
We present a patient who received nivolumab for heterogeneity of right-sided metastatic colon carcinoma. Intervention: The patient was treated with nivolumab combined with chemotherapy. Outcome: The computed tomography showed mass lesion in the left lobe of liver remained stable while metastasis tumors under envelop of liver were exacerbated after 6 cycles of nivolumab combined with chemotherapy, and later regressed. Lessons: The status of mismatch repair in primary tumor and metastatic liver carcinoma is contradictory but using nivolumab demonstrated encouraging efficacy. This is the first case of pseudo progress...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
GBM is the most aggressive form of brain cancer. The current standard of care against GBM is a combination of surgery, chemotherapy and radiotherapy. However, after standard treatment, the cancer usually recurs – emphasizing a need for new targets and better alternatives. A promising target is cyclin-dependent kinase 5 (CDK5), the hyperactivity of which has been shown to have a role in cancer progression. TP5/TFP5, a small peptide inhibitor against CDK5, was developed at the National Institutes of Health and modified to increase its passage through the blood brain barrier. Researchers at the NCI and NINDS demons...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
More News: Acetic Acid | Cancer | Cancer & Oncology | Carcinoma | Chemotherapy | Colon Cancer | Colorectal Cancer | Drugs & Pharmacology | Hormones | Investigational New Drugs | Study