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Illicit use of hCG in dietary programs and to promote anabolism
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<blockquote data-quote="madman" data-source="post: 245081" data-attributes="member: 13851"><p>Give you further insight as to where Cole is coming from.</p><p></p><p></p><p><strong>CHAPTER 30</strong></p><p><strong></strong></p><p><strong>Cancer hCG, hyperglycosylated hCG, extravillous cytotrophoblastic hCG, and TGFb receptor 2</strong></p><p></p><p><em><strong>One gonadotropin, extravillous cytotrophoblast hCG, is an apparent centerpiece of cancer.</strong> <strong>It is in fact stolen by cancers, from pregnancy, to drive malignancy.</strong> Extravillous cytotrophoblast hCG emerges from human evolution as a super acidic, super potent TGFß agonist [1–3]. <strong>Super acidic and super potent as a result of the evolution of an increasingly acidic hCG pathway (see Chapter 2) [1–3].</strong></em></p><p><em><strong></strong></em></p><p><em><strong>The story of hCG and cancer is a personal one and much of the research described below was performed in my own research groups or with collaborators [4–6].</strong> It started by looking at hCG as a tumor marker testing a total of 2,508 non-trophoblastic cancers (Including bladder cancer, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, gastric cancer, hepatic cancer, lung cancer, intestinal cancer, lymphoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, uterine cancer, and vulvar cancer) in <strong>first-morning urine samples.</strong> We also studied 91 trophoblastic cancers (choriocarcinoma, ovarian germ cell cancer, and testicular germ cell cancer) using<strong> first-morning urine samples and the B204 beta core fragment and nicked free ß-subunit assay (Table 30.1).</strong></em></p><p><em><strong></strong></em></p><p><em><strong>The 2,167 non-trophoblastic cancer patient urines and 91 trophoblastic cancer patient urine were tested in the B204 assay, with a 3.0 pmol/ml cancer cut-off.</strong> All 91 trophoblastic cancers were positive, 100% detection, yet only 949 of 2,167 non-trophoblastic cancer urines were positive, with 44% detection<strong> (Table 30.1). It was concluded that a more sensitive B204 assay was needed for non-trophoblastic cancers.</strong></em></p><p><em></em></p><p><em>A more sensitive assay was generated using 125I-tracer antibody and 1/12,000 rather than 1/4,000 capture antibody. <strong>The more sensitive assay had a cut-off for cancer of 0.1 pmol/ml. </strong>Using this assay, all 341 non-trophoblastic cancers were positive, with 100% detection. <strong>It was concluded that trophoblastic cancers produce larger amounts of detectable material, 3.5-2,398,000 pmol/ml or 1.3–880,000 mIU/ml, and that non-trophoblastic cancers produce tiny concentrations of detectable material, 0.2-340 pmol/ml or 0.074-124 mIU/ml. <u>We also concluded that all cancers produce one form of hCG or another</u>.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>But what form of hCG do cancers produce?</strong> Different hCG variants were measured using different assays: total hCG using the Siemens Immulite 1000 assay, hyperglycosylated hCG and extravillous cytotrophoblast hCG using the B152 assay, and all free ß-subunit using the FBT11 assay <strong>(Table 30.2).</strong></em></p><p><em></em></p><p><em>As shown in <strong>Table 30.2,</strong> 51 of 51 non-trophoblastic neoplasms serum samples, 100%, were positive in the Siemens Immulite assay, in the B152 (102 ± 6.5% of total hCG) and in the FBT11 assay (99 ± 8.8% of total hCG). <strong>This indicated that 51 of 51 cases were producing hyperglycosylated hCG or extravillous cytotrophoblast hCG free ß-subunit.</strong> Concanavalin A-Sepharose affinity chromatography (not shown) showed that the free ß-subunit had triantennary oligosaccharides or were extravillous cytotrophoblast free ß-subunit. Similarly, the total hCG and B152 immunoassays and the Concanavalin A-Sepharose test (not shown) indicated that 32 of 32 trophoblastic cancers were producing extravillous cytotrophoblast hCG. <strong>It was concluded that <u>trophoblastic cancer only (100%, no exceptions seen) produces extravillous cytotrophoblast hCG dimer and that non-trophoblastic cancer only (100%, no exceptions seen) produces extravillous cytotrophoblast hCG free ß-subunit</u>.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>Why were all non-trophoblastic cancers producing only beta subunit of hCG but all trophoblastic cancers were producing extravillous cytotrophoblast hCG? </strong>This question is best answered by a paper by Beebe et al [7]. In pregnancy, ß-subunit of hCG receives 6 disulfide bridges, and α-subunit of hCG receives 5 disulfide bridges. The last two disulfide bridges on ß-subunit, ß93-100 and ß26-110 are completed by a placental enzyme, placental disulfide isomerase.<strong> If hCG is produced by another cell other than a trophoblast cell, this enzyme is not present, and the disulfide bridges are not made. Without these disulfide bridges the ß-subunit just forms a free ß-subunit and does not combine with α-subunit to form αß dimer [7]. This was seemingly the case with cancer-free ß-subunit.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>Other authors have shown that the hCG molecules produced by cancer cells drove malignancy-like functions in cancer cells [8–15] (Table 30.3). Based on the studies described above, this must be extravillous cytotrophoblast hCG or its free ß-subunit.</strong> In 1996 Gillott et al. [8] showed that the ß-subunit produced by T24, ScaBER, and RT112 bladder cancer cell line drove cancer cell line growth and blocked apoptosis in. In 2000 this was confirmed by Butler et al. [9] using ScaBER bladder cancer cell line and its ß-subunit. In 2002 Devi et al. [10] tested DU145 prostate carcinoma cell line and showed that the ß-subunit drove cancer cell line growth. Then, in 2006 our laboratory [11] used Jar and JEG-III choriocarcinoma cell line and showed that invasive cytotrophoblast hCG drove cancer growth and drove cancer cell invasion of others. Then, in 2008 Jankowska et al. [12] showed with tissue from 12 patients with planoepithelial cervical cancer, with one patient with glossy cell cervical cancer, one patient with basaloid cell cervical cancer, one patient with intraepitheliate cervical cancer, and 15 patients with endometrial cancer that the ß-subunit blocked apoptosis. In 2008 Li et al. [13] showed with tissue from 81 patients with uterine cervical cancer that the ß-subunit blocked apoptosis and in 2011 Guo et al. [14] looked at T29 and T80 epithelial ovarian cancer cell lines and tissue from 15 patients with ovarian carcinoma and showed that the ß-subunit produced by the cancers promoted cell growth and blocked apoptosis. Finally, and most recently, Kawamata et al. [15] examined tissue from 80 patients with colorectal cancer, examined Caco-2, LoVo, HCA-7, WiDr, and T84 colorectal cancer cell lines, and showed with them all that ß-subunit drove cancer growth and drove cell-cell invasion of other tissues. <strong>All of these studies are summarized in Table 30.3.</strong></em></p><p><em></em></p><p><em>We went on to examine 10 different cancer cell lines, from choriocarcinoma, testicular germ cell cancer, endometrial adenocarcinoma, squamous bladder cancer, epithelial bladder carcinoma, epithelial lung cancer, Hodgkin’s lymphoma, and cervical carcinoma <strong>(Table 30.4). Again all 10 cancers produced extravillous cytotrophoblast hCG and its free ß-subunit and vast cancer cell growth. <u>It was concluded from these results (Tables 30.3 and 30.4), that extravillous cytotrophoblast hCG and its free ß-subunit seemingly drove malignancy in all or most cancers</u>.</strong></em></p><p><em></em></p><p><em>After the development of monoclonal antibody B152 (a monoclonal antibody raised against extravillous cytotrophoblast hCG and hyperglycosylated hCG and their free ß-subunit which did not bind the hormone hCG [16]), it was possible to immobilize extravillous cytotrophoblast hCG and its free ß-subunit as produced by cancer cell lines. <strong>As shown in Table 30.5 treatment with B152, 2.0 µg/ml, took the malignancy out of the cancer so that it did not grow at all over 24 hours. <u>Two conclusions were made</u>. <u>Firstly, this confirmed and proved that extravillous cytotrophoblast hCG and its free ß-subunit controlled malignancy in all or most cancers</u>. <u>Secondly, that this confirms that extravillous cytotrophoblast hCG and its free ß-subunit are the primary drivers of malignancy in cancer cells</u>.</strong></em></p><p><em></em></p><p><em>Furthermore, eight nude mice were transplanted subcutaneously with JEG-III human choriocarcinoma cells and 8 nude mice were transplanted subcutaneously with Caski human cervical carcinoma cells. In each transplant, 10 million cancer cells total were transplanted into 6 skin sites on nude mice. After two weeks, multiple metastases were present on the skin of animals, tumors as large as 2 cm in diameter in size. Athymic mice were then given either antibody B152 (2 × 4 mice) or control mouse immunoglobulin G (IgG) (2 × 4 mice), 0.3 mg intraperitoneally injected twice weekly for two weeks or until 4 weeks cancer time. The tumor cross-section area was measured weekly with calipers before every treatment according to the formula: length x width x π x 4. Termination was mandatory at 4 weeks for the University of New Mexico Health Science Center Animal Resource Center.</em></p><p><em></em></p><p><em><strong>As shown in Fig. 30.1, IgG did nothing but let both cancers continue to grow and metastasize to >300% of two weeks' size. B152 immediately blocked the cancers, blocking all cancer malignancies.</strong> After 4 weeks the choriocarcinoma was if anything 76% the size of the cancer at 2 weeks cancer time, and the cervical cancer was if anything 91% of the size of the cancer at 2 weeks.</em></p><p></p><p><strong><em>In conclusion, B152 antibody treatment eliminated the malignancy of the human choriocarcinoma (Fig. 30.2A) and of the human cervical carcinoma (Fig. 30.2B) in athymic mice, deactivated the cancer.</em></strong></p><p></p><p><em><strong>Extravillous cytotrophoblast hCG and its free ß-subunit blocks apoptosis in human cancer cases (Table 30.3) and blocks immune response to the cancer.</strong> If B152 was humanized by established DNA technology [17–19], B152 would possibly be an effective cure for cancer, blocking malignancy and without extravillous cytotrophoblast hCG or its free ß-subunit apoptosis and the immune system would destroy all remnant cancer tissue. <strong>Alternatively put, B152 could be a cure for all or most human cancers, and removing these forms of hCG from the circulation could present a very interesting therapy for treating cancers that produce these molecules [20] and that specific antibody therapies will need to take into consideration glycovariation on hCG to ensure effectiveness [21].</strong></em></p><p><em><strong></strong></em></p><p><em><strong>We know that the production of hCG is linked to the growth and invasion in cancer cells but what is the mode of action?</strong> Multiple authors have shown that the ß-subunit of hyperglycosylated hCG and extravillous cytotrophoblast hCG and free ß-subunit act on TGFß receptor 2. <strong>It is through this receptor that hCG can block apoptosis, promote cell growth and promote invasion by promoting metalloproteinases and promoting collagenases [9, 22, 23].</strong></em></p><p><em></em></p><p><em>Interestingly, Butler and colleagues [9] who tested TGFß receptor 2 activity in bladder cancer cells claim that hCG free ß-subunit are antagonists and can be specifically competed out. Berndt and colleagues [22] used LHCGR mouse aortic ring cells and insist that it is an agonist. Ahmad and colleagues found that overall hCG ß-subunit formed a special previously unknown link with TGFß that changed everything. <strong>Whatever this previously unknown link may be, it allows the hCG ß-subunit to take control of the TGFß receptor.</strong></em></p><p><em><strong></strong></em></p><p><em><strong>A model of hyperglycosylated hCG, hyperglycosylated hCG free β-subunit, or hCG free β-subunit antagonizing cytotrophoblast cells in blastocyst implantation or cancer malignancies is shown in Fig. 30.1. </strong>As illustrated, TGFβ-II receptors act through SMAD and cAMP intermediates, which permit nuclear penetration. SMADs have been demonstrated in the response of TGFβ receptor 2 to hyperglycosylated hCG [22]. Angiogenesis has also been demonstrated in response to hyperglycosylated hCG [23] and that hyperglycosylated hCG and hyperglycosylated hCG free β-subunit are interchangeable promoters with similar potency have also been demonstrated [24].</em></p><p><em></em></p><p><em>Lustabader et al., Lapthorn et al., and Wu et al. [25–28] have demonstrated a common cystine knot structure in hCG (on hCG α-subunit and β-subunit) linking the structure of hCG and TGFβ. <strong>That the hCG amino acid sequence with different glycosylation (hyperglycosylation) can bind the LH/hCG hormone receptor and the TGFβ-II autocrine receptor is rather unusual, giving the molecule two distinctly different functions (hCG and hyperglycosylated hCG) and two distinct sets of actions. These mechanisms and actions of hCGβ in epithelial cancer were proposed almost twenty years ago [29] and have since been discussed in detail by Butler and collaborators [30,31].</strong></em></p><p></p><p></p><p></p><p></p><p><strong>Table 30.1 Urine B204 assay (cancer cut-off 3.0 pmol/ml) and super-sensitive B204 assay (cancer cut-off 0.1 pmol/ml), detects ß-core fragment, free ß-subunit, hyperglycosylated hCG free ß-subunit and nicked free ß-subunit.</strong></p><p><strong>[ATTACH=full]28857[/ATTACH]</strong></p><p><strong>[ATTACH=full]28858[/ATTACH]</strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong>Table 30.2 Content of cancer patient serum, measured using Immulite total hCG assay, B152 hyperglycosylated molecule assay, and FBT11 free ß-subunit assay.</strong></p><p><strong>[ATTACH=full]28859[/ATTACH]</strong></p><p><strong>[ATTACH=full]28860[/ATTACH]</strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong>Table 30.2 Content of cancer patient serum, measured using Immulite total hCG assay, B152 hyperglycosylated molecule assay, and FBT11 free ß-subunit assay.</strong></p><p><strong>[ATTACH=full]28861[/ATTACH]</strong></p><p><strong>[ATTACH=full]28862[/ATTACH]</strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong>Table 30.2 Content of cancer patient serum, measured using Immulite total hCG assay, B152 hyperglycosylated molecule assay, and FBT11 free ß-subunit assay. (Cont.)</strong></p><p><strong>[ATTACH=full]28864[/ATTACH]</strong></p><p><strong>[ATTACH=full]28865[/ATTACH]</strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong></strong></p><p><strong>Table 30.3 Eight independent reports that hyperglycosylated hCG and hCG ß-subunit promote cancer cell malignancy (10-17).</strong></p><p><strong>[ATTACH=full]28866[/ATTACH]</strong></p></blockquote><p></p>
[QUOTE="madman, post: 245081, member: 13851"] Give you further insight as to where Cole is coming from. [B]CHAPTER 30 Cancer hCG, hyperglycosylated hCG, extravillous cytotrophoblastic hCG, and TGFb receptor 2[/B] [I][B]One gonadotropin, extravillous cytotrophoblast hCG, is an apparent centerpiece of cancer.[/B] [B]It is in fact stolen by cancers, from pregnancy, to drive malignancy.[/B] Extravillous cytotrophoblast hCG emerges from human evolution as a super acidic, super potent TGFß agonist [1–3]. [B]Super acidic and super potent as a result of the evolution of an increasingly acidic hCG pathway (see Chapter 2) [1–3]. The story of hCG and cancer is a personal one and much of the research described below was performed in my own research groups or with collaborators [4–6].[/B] It started by looking at hCG as a tumor marker testing a total of 2,508 non-trophoblastic cancers (Including bladder cancer, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, gastric cancer, hepatic cancer, lung cancer, intestinal cancer, lymphoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, uterine cancer, and vulvar cancer) in [B]first-morning urine samples.[/B] We also studied 91 trophoblastic cancers (choriocarcinoma, ovarian germ cell cancer, and testicular germ cell cancer) using[B] first-morning urine samples and the B204 beta core fragment and nicked free ß-subunit assay (Table 30.1). The 2,167 non-trophoblastic cancer patient urines and 91 trophoblastic cancer patient urine were tested in the B204 assay, with a 3.0 pmol/ml cancer cut-off.[/B] All 91 trophoblastic cancers were positive, 100% detection, yet only 949 of 2,167 non-trophoblastic cancer urines were positive, with 44% detection[B] (Table 30.1). It was concluded that a more sensitive B204 assay was needed for non-trophoblastic cancers.[/B] A more sensitive assay was generated using 125I-tracer antibody and 1/12,000 rather than 1/4,000 capture antibody. [B]The more sensitive assay had a cut-off for cancer of 0.1 pmol/ml. [/B]Using this assay, all 341 non-trophoblastic cancers were positive, with 100% detection. [B]It was concluded that trophoblastic cancers produce larger amounts of detectable material, 3.5-2,398,000 pmol/ml or 1.3–880,000 mIU/ml, and that non-trophoblastic cancers produce tiny concentrations of detectable material, 0.2-340 pmol/ml or 0.074-124 mIU/ml. [U]We also concluded that all cancers produce one form of hCG or another[/U]. But what form of hCG do cancers produce?[/B] Different hCG variants were measured using different assays: total hCG using the Siemens Immulite 1000 assay, hyperglycosylated hCG and extravillous cytotrophoblast hCG using the B152 assay, and all free ß-subunit using the FBT11 assay [B](Table 30.2).[/B] As shown in [B]Table 30.2,[/B] 51 of 51 non-trophoblastic neoplasms serum samples, 100%, were positive in the Siemens Immulite assay, in the B152 (102 ± 6.5% of total hCG) and in the FBT11 assay (99 ± 8.8% of total hCG). [B]This indicated that 51 of 51 cases were producing hyperglycosylated hCG or extravillous cytotrophoblast hCG free ß-subunit.[/B] Concanavalin A-Sepharose affinity chromatography (not shown) showed that the free ß-subunit had triantennary oligosaccharides or were extravillous cytotrophoblast free ß-subunit. Similarly, the total hCG and B152 immunoassays and the Concanavalin A-Sepharose test (not shown) indicated that 32 of 32 trophoblastic cancers were producing extravillous cytotrophoblast hCG. [B]It was concluded that [U]trophoblastic cancer only (100%, no exceptions seen) produces extravillous cytotrophoblast hCG dimer and that non-trophoblastic cancer only (100%, no exceptions seen) produces extravillous cytotrophoblast hCG free ß-subunit[/U]. Why were all non-trophoblastic cancers producing only beta subunit of hCG but all trophoblastic cancers were producing extravillous cytotrophoblast hCG? [/B]This question is best answered by a paper by Beebe et al [7]. In pregnancy, ß-subunit of hCG receives 6 disulfide bridges, and α-subunit of hCG receives 5 disulfide bridges. The last two disulfide bridges on ß-subunit, ß93-100 and ß26-110 are completed by a placental enzyme, placental disulfide isomerase.[B] If hCG is produced by another cell other than a trophoblast cell, this enzyme is not present, and the disulfide bridges are not made. Without these disulfide bridges the ß-subunit just forms a free ß-subunit and does not combine with α-subunit to form αß dimer [7]. This was seemingly the case with cancer-free ß-subunit. Other authors have shown that the hCG molecules produced by cancer cells drove malignancy-like functions in cancer cells [8–15] (Table 30.3). Based on the studies described above, this must be extravillous cytotrophoblast hCG or its free ß-subunit.[/B] In 1996 Gillott et al. [8] showed that the ß-subunit produced by T24, ScaBER, and RT112 bladder cancer cell line drove cancer cell line growth and blocked apoptosis in. In 2000 this was confirmed by Butler et al. [9] using ScaBER bladder cancer cell line and its ß-subunit. In 2002 Devi et al. [10] tested DU145 prostate carcinoma cell line and showed that the ß-subunit drove cancer cell line growth. Then, in 2006 our laboratory [11] used Jar and JEG-III choriocarcinoma cell line and showed that invasive cytotrophoblast hCG drove cancer growth and drove cancer cell invasion of others. Then, in 2008 Jankowska et al. [12] showed with tissue from 12 patients with planoepithelial cervical cancer, with one patient with glossy cell cervical cancer, one patient with basaloid cell cervical cancer, one patient with intraepitheliate cervical cancer, and 15 patients with endometrial cancer that the ß-subunit blocked apoptosis. In 2008 Li et al. [13] showed with tissue from 81 patients with uterine cervical cancer that the ß-subunit blocked apoptosis and in 2011 Guo et al. [14] looked at T29 and T80 epithelial ovarian cancer cell lines and tissue from 15 patients with ovarian carcinoma and showed that the ß-subunit produced by the cancers promoted cell growth and blocked apoptosis. Finally, and most recently, Kawamata et al. [15] examined tissue from 80 patients with colorectal cancer, examined Caco-2, LoVo, HCA-7, WiDr, and T84 colorectal cancer cell lines, and showed with them all that ß-subunit drove cancer growth and drove cell-cell invasion of other tissues. [B]All of these studies are summarized in Table 30.3.[/B] We went on to examine 10 different cancer cell lines, from choriocarcinoma, testicular germ cell cancer, endometrial adenocarcinoma, squamous bladder cancer, epithelial bladder carcinoma, epithelial lung cancer, Hodgkin’s lymphoma, and cervical carcinoma [B](Table 30.4). Again all 10 cancers produced extravillous cytotrophoblast hCG and its free ß-subunit and vast cancer cell growth. [U]It was concluded from these results (Tables 30.3 and 30.4), that extravillous cytotrophoblast hCG and its free ß-subunit seemingly drove malignancy in all or most cancers[/U].[/B] After the development of monoclonal antibody B152 (a monoclonal antibody raised against extravillous cytotrophoblast hCG and hyperglycosylated hCG and their free ß-subunit which did not bind the hormone hCG [16]), it was possible to immobilize extravillous cytotrophoblast hCG and its free ß-subunit as produced by cancer cell lines. [B]As shown in Table 30.5 treatment with B152, 2.0 µg/ml, took the malignancy out of the cancer so that it did not grow at all over 24 hours. [U]Two conclusions were made[/U]. [U]Firstly, this confirmed and proved that extravillous cytotrophoblast hCG and its free ß-subunit controlled malignancy in all or most cancers[/U]. [U]Secondly, that this confirms that extravillous cytotrophoblast hCG and its free ß-subunit are the primary drivers of malignancy in cancer cells[/U].[/B] Furthermore, eight nude mice were transplanted subcutaneously with JEG-III human choriocarcinoma cells and 8 nude mice were transplanted subcutaneously with Caski human cervical carcinoma cells. In each transplant, 10 million cancer cells total were transplanted into 6 skin sites on nude mice. After two weeks, multiple metastases were present on the skin of animals, tumors as large as 2 cm in diameter in size. Athymic mice were then given either antibody B152 (2 × 4 mice) or control mouse immunoglobulin G (IgG) (2 × 4 mice), 0.3 mg intraperitoneally injected twice weekly for two weeks or until 4 weeks cancer time. The tumor cross-section area was measured weekly with calipers before every treatment according to the formula: length x width x π x 4. Termination was mandatory at 4 weeks for the University of New Mexico Health Science Center Animal Resource Center. [B]As shown in Fig. 30.1, IgG did nothing but let both cancers continue to grow and metastasize to >300% of two weeks' size. B152 immediately blocked the cancers, blocking all cancer malignancies.[/B] After 4 weeks the choriocarcinoma was if anything 76% the size of the cancer at 2 weeks cancer time, and the cervical cancer was if anything 91% of the size of the cancer at 2 weeks.[/I] [B][I]In conclusion, B152 antibody treatment eliminated the malignancy of the human choriocarcinoma (Fig. 30.2A) and of the human cervical carcinoma (Fig. 30.2B) in athymic mice, deactivated the cancer.[/I][/B] [I][B]Extravillous cytotrophoblast hCG and its free ß-subunit blocks apoptosis in human cancer cases (Table 30.3) and blocks immune response to the cancer.[/B] If B152 was humanized by established DNA technology [17–19], B152 would possibly be an effective cure for cancer, blocking malignancy and without extravillous cytotrophoblast hCG or its free ß-subunit apoptosis and the immune system would destroy all remnant cancer tissue. [B]Alternatively put, B152 could be a cure for all or most human cancers, and removing these forms of hCG from the circulation could present a very interesting therapy for treating cancers that produce these molecules [20] and that specific antibody therapies will need to take into consideration glycovariation on hCG to ensure effectiveness [21]. We know that the production of hCG is linked to the growth and invasion in cancer cells but what is the mode of action?[/B] Multiple authors have shown that the ß-subunit of hyperglycosylated hCG and extravillous cytotrophoblast hCG and free ß-subunit act on TGFß receptor 2. [B]It is through this receptor that hCG can block apoptosis, promote cell growth and promote invasion by promoting metalloproteinases and promoting collagenases [9, 22, 23].[/B] Interestingly, Butler and colleagues [9] who tested TGFß receptor 2 activity in bladder cancer cells claim that hCG free ß-subunit are antagonists and can be specifically competed out. Berndt and colleagues [22] used LHCGR mouse aortic ring cells and insist that it is an agonist. Ahmad and colleagues found that overall hCG ß-subunit formed a special previously unknown link with TGFß that changed everything. [B]Whatever this previously unknown link may be, it allows the hCG ß-subunit to take control of the TGFß receptor. A model of hyperglycosylated hCG, hyperglycosylated hCG free β-subunit, or hCG free β-subunit antagonizing cytotrophoblast cells in blastocyst implantation or cancer malignancies is shown in Fig. 30.1. [/B]As illustrated, TGFβ-II receptors act through SMAD and cAMP intermediates, which permit nuclear penetration. SMADs have been demonstrated in the response of TGFβ receptor 2 to hyperglycosylated hCG [22]. Angiogenesis has also been demonstrated in response to hyperglycosylated hCG [23] and that hyperglycosylated hCG and hyperglycosylated hCG free β-subunit are interchangeable promoters with similar potency have also been demonstrated [24]. Lustabader et al., Lapthorn et al., and Wu et al. [25–28] have demonstrated a common cystine knot structure in hCG (on hCG α-subunit and β-subunit) linking the structure of hCG and TGFβ. [B]That the hCG amino acid sequence with different glycosylation (hyperglycosylation) can bind the LH/hCG hormone receptor and the TGFβ-II autocrine receptor is rather unusual, giving the molecule two distinctly different functions (hCG and hyperglycosylated hCG) and two distinct sets of actions. These mechanisms and actions of hCGβ in epithelial cancer were proposed almost twenty years ago [29] and have since been discussed in detail by Butler and collaborators [30,31].[/B][/I] [B]Table 30.1 Urine B204 assay (cancer cut-off 3.0 pmol/ml) and super-sensitive B204 assay (cancer cut-off 0.1 pmol/ml), detects ß-core fragment, free ß-subunit, hyperglycosylated hCG free ß-subunit and nicked free ß-subunit. [ATTACH type="full" alt="Screenshot (20291).png"]28857[/ATTACH] [ATTACH type="full" alt="Screenshot (20292).png"]28858[/ATTACH] Table 30.2 Content of cancer patient serum, measured using Immulite total hCG assay, B152 hyperglycosylated molecule assay, and FBT11 free ß-subunit assay. [ATTACH type="full" alt="Screenshot (20293).png"]28859[/ATTACH] [ATTACH type="full" alt="Screenshot (20294).png"]28860[/ATTACH] Table 30.2 Content of cancer patient serum, measured using Immulite total hCG assay, B152 hyperglycosylated molecule assay, and FBT11 free ß-subunit assay. [ATTACH type="full" alt="Screenshot (20295).png"]28861[/ATTACH] [ATTACH type="full" alt="Screenshot (20296).png"]28862[/ATTACH] Table 30.2 Content of cancer patient serum, measured using Immulite total hCG assay, B152 hyperglycosylated molecule assay, and FBT11 free ß-subunit assay. (Cont.) [ATTACH type="full" alt="Screenshot (20297).png"]28864[/ATTACH] [ATTACH type="full" alt="Screenshot (20298).png"]28865[/ATTACH] Table 30.3 Eight independent reports that hyperglycosylated hCG and hCG ß-subunit promote cancer cell malignancy (10-17). [ATTACH type="full" alt="Screenshot (20299).png"]28866[/ATTACH][/B] [/QUOTE]
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Illicit use of hCG in dietary programs and to promote anabolism
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