Disease relevance of INSL6

• KHT and RIF-1 murine sarcomas, the HT29 human colon carcinoma, and the HX118 human melanoma tumors were studied [1].
• Metastatic behavior of the RIF-1 murine fibrosarcoma: inhibited by hypophysectomy and partially restored by growth hormone replacement [2].
• To measure intertumor heterogeneity, two murine sarcomas (RIF-1 and KHT) and two human ovarian carcinoma xenografts (OWI and MLS) were utilized [3].
• Histological sections of the RIF-1 tumors revealed intravascular congestion by 2 h, extravascular hemorrhage by 4 h, and necrosis by 12 h after treatment with IL-1 alpha [4].
• The effect of simultaneous whole-body heat (45 min 41 degrees C) on cyclophosphamide (CTX) and BCNU toxicity to normal mouse marrow stem cells and to the RIF-1 tumour in C3H/He mice has been studied [5].

High impact information on INSL6

• RESULTS: Hydralazine significantly reduced the 19F signal intensity in the murine tumors RIF-1 and KHT and in the HT29 human tumor, with little reduction in the SCCVII/Ha murine and HX118 human tumors [1].
• Treatment with the tumor necrosis factor-alpha-inducing drug 5,6-dimethylxanthenone-4-acetic acid enhances the antitumor activity of the photodynamic therapy of RIF-1 mouse tumors [6].
• We have recently demonstrated evidence of IGF dependency in murine MGH-OGS and RIF-1 sarcomas, which express relatively high and intermediate levels of IGF-1 receptors [7].
• This study shows that a Photofrin-induced photodynamic therapy-resistant variant (RIF-8A) of a radiation-induced fibrosarcoma-1 cell line (RIF-1) is cross-resistant to cis-diamminedichloroplatinum(II) (cisplatin) [8].
• Immediately following a 1-h exposure to cisplatin (50 microM), RIF-1 cells contained 44.6 +/- 2.0 (SEM) pg platinum/micrograms DNA while RIF-8A cells contained 24.8 +/- 6.3 pg platinum/micrograms DNA [8].

Chemical compound and disease context of INSL6

• The thymidine labeling index of RIF-1 fibrosarcoma was not affected by interleukin 1 injection [9].
• 5-chlorodeoxycytidine, a radiosensitizer effective against RIF-1 and Lewis lung carcinoma, is also effective against a DMBA-induced mammary adenocarcinoma and the EMT-6 tumor in BALB/c mice [10].
• Following the NMR experiment, tumors were chemically assayed for lactate giving 8.17, 9.1, and 6.73 mumols/g wet wt for RIF-1, EMT6, and fibroma, respectively [11].
• In two mouse tumours, the RIF-1 fibrosarcoma and the human xenograft HT29, carbogen breathing induced a transient fall in signal intensity that reversed spontaneously within a few minutes [12].
• A marked decrease in betaNTP/Pi and pH was observed in both the RIF-1 fibrosarcoma and the third-generation T115 mammary carcinoma after hydralazine challenge [13].

Biological context of INSL6

• A new member of the insulin gene family (INSL6) was identified from an Expressed Sequence Tag database through a search for proteins containing the insulin family B-chain cysteine motif [14].
• The time course of bioenergetic changes in RIF-1 tumors determined by 31P-NMR spectroscopy was found to parallel the reduction and subsequent recovery of tumor blood flow [4].
• The present experiments were conducted to determine the effects of cyclophosphamide (150 mg/kg) on the pathophysiology of RIF-1 solid tumors and to determine the temporal relationship between treatment mediated changes in tumor vascular physiology, cell proliferation, and chemoresponsiveness in vivo [15].
• The resistance factors relative to RIF-1, calculated from full survival curves for cis-DDP, were 3.8 +/- 0.4 for Chinese hamster ovary cells and 8.8 +/- 0.7 for both A2780 and A1847 lines [16].
• The kinetics of cis-DDP-DNA adduct formation and loss was investigated in RIF-1, A2780, and A1847 cells by the immunocytochemistry technique [16].

Anatomical context of INSL6

• Identification of INSL6, a new member of the insulin family that is expressed in the testis of the human and rat [14].
• INSL6 was found to be expressed at high levels in the testis as determined by Northern blot analysis and specifically within the seminiferous tubules in spermatocytes and round spermatids as detected by in situ hybridization analysis [14].
• Up to 3.9% replacement of thymidine by CldU took place in RIF-1 tumors, whereas incorporation into bone marrow was below our limit of detection [17].
• Differences between RIF-1 and RIF-8A in the competitive mitochondrial binding of NAO or Rh-123 with Photofrin suggest that the inner mitochondrial membrane is a significant Photofrin binding site [18].
• The goal of this study was to investigate the heat sensitivity of the microcirculation in normal C3H murine leg muscle and a variety of transplanted tumour lines (KHT, SCC-VII, RIF-1, C3H mouse mammary carcinoma, two human mammary carcinomas MDA-468 and S5) [19].

Associations of INSL6 with chemical compounds

• In split-dose experiments, the time-dependent increases in the chemoresponsiveness of RIF-1 tumors, after cyclophosphamide, may be due not only to the increased proliferation of repopulating cells, but also to vascular responses attendant with cytoreduction [15].
• In vitro, ketoconazole and IL-1 alpha induced only additive clonogenic cell kill in primary RIF-1 explant cultures [20].
• Resistance does not appear to be the result of elevated glutathione levels since neither the resistant variant (RIF-8A) nor the parental line (RIF-1) varied in total glutathione levels [8].
• The effect of elevated plasma corticosterone levels, induced by ketamine-acepromazine anesthesia, on IL-1 alpha responsiveness was also studied in the RIF-1 tumor model [20].
• METHODS: A WAF1/iNOS/liposome complex was injected directly into RIF-1 and HT29 tumours in mice [21].

Other interactions of INSL6

• Human INSL6 was 43% identical to human relaxin H2 in the B- and A-chain regions [14].
• The exclusive expression pattern of RIF1 and related RLF in testis interstitial cells suggested potential physiological roles of these two distinct insulin/relaxin family ligands in testis function [22].
• IL-1 alpha produced dose-dependent sensitization of clonogenic RIF-1 tumor cells to MMC in vivo [23].
• Cell proliferation in RIF-1 tumors, assessed by [3H]thymidine labeling index and tumor growth fraction (primer-dependent DNA polymerase labeling assay) measurements, was inhibited for up to 3 days by cyclophosphamide [15].

Analytical, diagnostic and therapeutic context of INSL6

• Northern blot analysis showed that RIF1 transcripts are approximately 1.2 kb in size and are expressed mainly in testis of mouse and human [22].
• After RT-PCR, full-length cDNAs of RIF1 and RIF2 were obtained from mouse testis and ovary, respectively [22].
• The IL-1-mediated hemorrhagic response was maximal 6-12 h after treatment and greater in Panc02 tumors than in RIF-1 tumors [24].
• The volume-dependence of the HbO2 saturation status differed similarly among the tumor lines; HbO2 saturation status decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines and was independent of tumor volume for the OWI line [25].
• In s.c. RIF-1 tumors (C3H/HeJ mice) ketoconazole potentiated IL-1 alpha induced hemorrhagic necrosis (59Fe labeled RBC uptake) and prolonged intervals of low tumor perfusion (86Rb+ uptake) and attendant depletion of tumor high energy phosphate reserves as determined by in vivo 31P nuclear magnetic resonance spectroscopy [20].

References