Development of an Active Site Peptide Analog of α-Fetoprotein That Prevents Breast Cancer

Jacobson, Herbert I.; Andersen, Thomas T.; Bennett, James A.

doi:10.1158/1940-6207.capr-13-0405

Cited by 11 publications

(4 citation statements)

References 60 publications

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“…11 , 12 In addition, the maternal serum alpha-fetoprotein (AFP) level was high during pregnancy, and the AFP had direct antibreast cancer activity. 13 , 14 Therefore, the age at diagnosis of breast cancer increased with increased parity. Albrektsen et al 15 found that women with multiparity had a slightly lower risk of breast cancer compared with women with parity 1.…”

Section: Discussionmentioning

confidence: 99%

Parity association with clinicopathological factors in invasive breast cancer: a retrospective analysis

Shen¹,

Zhang

Xiao

et al. 2017

OTT

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The aim of this study was to determine the relationship between parity and age at diagnosis, primary tumor size, axillary lymph node (ALN) metastasis, histological grade, and subtype classification in patients with breast cancer. Data from 392 patients with invasive breast cancer were collected and divided into four groups: nulliparous (parity 0), parity 1, parity 2, and parity ≥3. The relationship between parity and age at diagnosis was assessed using post hoc Dunnett’s T3 test, and tumor size, the number of ALN metastases, and histological grade were analyzed using Spearman’s rho test. Breast cancer subtypes were analyzed using the chi-square (χ2) test. The results showed that the mean age at diagnosis increased with increased parity, and the mean age of patients with parity ≥3 was significantly greater than that of patients with parity 0, parity 1, and parity 2. The mean age at diagnosis of patients with parity 2 was greater than that of patients with parity 1. There was no significant difference in the mean age between patients with parity 0 and parity 1 or parity 0 and parity 2. Parity was negatively correlated with ALN metastasis. Parity was not correlated with tumor size or histological grade and the proportion of the four subtypes in breast cancer. So, increased parity deferred the onset of breast cancer and inhibited the metastasis of ALN, but did not affect tumor size, histological grade, or the proportion of subtypes. Increased parity was a protective factor against breast cancer.

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Section: Discussionmentioning

confidence: 99%

Parity association with clinicopathological factors in invasive breast cancer: a retrospective analysis

Shen¹,

Zhang

Xiao

et al. 2017

OTT

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“…However, when the enzyme active site is considered, its role in cancer is also dependent on the feature of the protein (oncogene or tumor suppressor gene). For example, in breast cancer, overexpression of BCRP (breast cancer resistance protein) with its intact active site could cause drug resistance, while mutation in the active site of α-fetoprotein (AFP) could reduce breast cancer risk 46 . These mutations can impact enzymes to metabolize different substrates 47 , leading to pathological processes.…”

Section: Resultsmentioning

confidence: 99%

Distribution bias analysis of germline and somatic single-nucleotide variations that impact protein functional site and neighboring amino acids

Pan

Cheng

et al. 2017

Sci Rep

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Single nucleotide variations (SNVs) can result in loss or gain of protein functional sites. We analyzed the effects of SNVs on enzyme active sites, ligand binding sites, and various types of post translational modification (PTM) sites. We found that, for most types of protein functional sites, the SNV pattern differs between germline and somatic mutations as well as between synonymous and non-synonymous mutations. From a total of 51,138 protein functional site affecting SNVs (pfsSNVs), a pan-cancer analysis revealed 142 somatic pfsSNVs in five or more cancer types. By leveraging patient information for somatic pfsSNVs, we identified 17 loss of functional site SNVs and 60 gain of functional site SNVs which are significantly enriched in patients with specific cancer types. Of the key pfsSNVs identified in our analysis above, we highlight 132 key pfsSNVs within 17 genes that are found in well-established cancer associated gene lists. For illustrating how key pfsSNVs can be prioritized further, we provide a use case where we performed survival analysis showing that a loss of phosphorylation site pfsSNV at position 105 in MEF2A is significantly associated with decreased pancreatic cancer patient survival rate. These 132 pfsSNVs can be used in developing genetic testing pipelines.

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“…Thus, the reason for the high levels of AFP when a diagnosis of breast cancer is established and other diseases are ruled out remains unexplained. Although studies have shown that AFP has endocrine effects that may reduce the risk of estrogen-dependent breast cancer ( 14 ), it is obviously not applicable to this patient. If we assume that the occurrence of PNECB promoted AFP secretion, then AFP levels should have declined at the postoperative assessment points; yet, there was no reduction in post-treatment AFP levels.…”

Section: Discussionmentioning

confidence: 99%

Primary neuroendocrine carcinoma of the breast with markedly elevated alpha-fetoprotein: a case report

Wang¹,

Wang²,

Du³

et al. 2021

Transl Cancer Res TCR

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Primary neuroendocrine carcinoma of the breast (PNECB) is a relatively rare subtype of breast cancer that has seldom been studied since its initial description. At present, the pathogenesis of the disease remains unknown, and there exit no specific clinical guidelines or specifications for its diagnosis and treatment. In addition, alpha-fetoprotein (AFP)-despite being a tumor marker-plays a small role in the diagnosis of breast cancer. Here, we explain the diagnosis and treatment of primary neuroendocrine (NE) breast carcinoma in a patient with a markedly elevated level of AFP. A 52-year-old woman visited our hospital, reporting she had palpated a nodule in her left breast 1 day before admission. After ultrasonographic detection of the hypoechoic lesion in her left breast-which was classified according to the Breast Imaging Reporting and Data System (BI-RADS) as grade 4C-and the abnormal enlargement of her left axillary lymph nodes, the patient was referred to our department as a case of malignant breast tumor. Meanwhile, the level of the tumor marker AFP was found to be over 1,210 ng/mL (0-7 ng/mL). And the patient had no past medical history of increased AFP, abnormal liver function, or gastrointestinal tumor. Analysis of the surgical specimens obtained from the left breast showed grade II invasive ductal carcinoma with NE differentiation.After discussion with a multidisciplinary team (MDT), according to the results of pathological and immunohistochemical examinations, the patient was diagnosed with PNECB. Due to axillary lymph node metastasis, she received combined chemotherapy with cyclophosphamide, epirubicin, and paclitaxel on postoperative day 13. Up to now, six cycles of chemotherapy have been successfully administered, with no evidence of adverse reactions. AFP levels were all above 1,210 ng/mL during chemotherapy. At the time of submission, the patient has been followed up for 10 months and there has been axillary lymph node metastasis, but no tumors in other parts have been found. Therefore, we think that the increase in AFP levels is related to the occurrence and poor prognosis of PNECB.

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Development of an Active Site Peptide Analog of α-Fetoprotein That Prevents Breast Cancer

Cited by 11 publications

References 60 publications

Parity association with clinicopathological factors in invasive breast cancer: a retrospective analysis

Parity association with clinicopathological factors in invasive breast cancer: a retrospective analysis

Distribution bias analysis of germline and somatic single-nucleotide variations that impact protein functional site and neighboring amino acids

Primary neuroendocrine carcinoma of the breast with markedly elevated alpha-fetoprotein: a case report

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