Influence of sex hormones on pancreatic Cancer

Andrén‐Sandberg, Åke; Johansson, Jan

doi:10.1007/bf02924234

Cited by 13 publications

(3 citation statements)

References 34 publications

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“…However, as is evident from our in vivo data, drug efficacy in female animals is heavily confounded by sex-specific factors (Figure 4E). Indeed, PDAC cells have been found to express sex hormone receptors [69,70] and it has been shown that β-estradiol can sensitize PDAC cells to chemotherapy [71]. Interestingly, we observed the opposite effect in vitro.…”

Section: Discussionmentioning

confidence: 46%

Sex Matters–Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer

Schulz,

Leitner,

Schreiber

et al. 2024

Cancers

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Preclinical studies rarely test the efficacy of therapies in both sexes. The field of oncology is no exception in this regard. In a model of syngeneic, orthotopic, metastasized pancreatic ductal adenocarcinoma we evaluated the impact of sex on pathological features of this disease as well as on the efficacy and possible adverse side effects of a novel, small molecule-based therapy inhibiting KRAS:SOS1, MEK1/2 and PI3K signaling in male and female C57BL/6J mice. Male mice had less tumor infiltration of CD8-positive cells, developed bigger tumors, had more lung metastasis and a lower probability of survival compared to female mice. These more severe pathological features in male animals were accompanied by higher distress at the end of the experiment. The evaluated inhibitors BI-3406, trametinib and BKM120 showed synergistic effects in vitro. This combinatorial therapy reduced tumor weight more efficiently in male animals, although the drug concentrations were similar in the tumors of both sexes. These results underline the importance of sex-specific preclinical research and at the same time provide a solid basis for future studies with the tested compounds.

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Section: Discussionmentioning

confidence: 46%

Sex Matters–Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer

Schulz,

Leitner,

Schreiber

et al. 2024

Cancers

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“…7 This observation, along with the epidemiological observations regarding deviating incidences in females, pregnancy, and oral contraceptive administration, 8 as well as the histological observation of presence of ovarian-type stroma in pancreatic lesions, 9 quickly created optimism that a novel therapeutic approach in pancreatic cancer might emerge. [10][11][12] However, initial enthusiasm was succeeded by skepticism, as early studies did not demonstrate a significant impact with tamoxifen treatment in unresectable pancreatic ductal adenocarcinoma. 13,14 Consequently, research interest declined until Mosselman et al 15 identified another isoform of the ER, leading to the differentiation of ER-α and ER-β.…”

mentioning

confidence: 99%

“…Gradually, research revealed that estrogens are involved in the endocrine function of β cells 6 but also in the tumorigenesis of several types of pancreatic neoplasms 7 . This observation, along with the epidemiological observations regarding deviating incidences in females, pregnancy, and oral contraceptive administration, 8 as well as the histological observation of presence of ovarian-type stroma in pancreatic lesions, 9 quickly created optimism that a novel therapeutic approach in pancreatic cancer might emerge 10–12 . However, initial enthusiasm was succeeded by skepticism, as early studies did not demonstrate a significant impact with tamoxifen treatment in unresectable pancreatic ductal adenocarcinoma 13,14 .…”

mentioning

confidence: 99%

Estrogen Receptor Expression in Pancreatic Adenocarcinoma

Lykoudis

Contis

2021

Pancreas

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Pancreatic adenocarcinoma remains a chemotherapy-resistant and refractory malignancy with high mortality, unaffected by recent progress in anticancer treatment. Expression of estrogen receptors was detected almost 50 years ago, in both benign and malignant pancreatic cells. However, early preclinical studies in pancreatic cancer led to contradictory findings, and most clinical studies failed to demonstrate an effect with tamoxifen treatment. The identification of a second form of estrogen receptor seems to provide some explanation for these discrepancies. Predominantly expressed in malignant cells and structurally different from what was considered the only estrogen receptor, estrogen receptor β was recognized as a negative prognostic factor and a possible therapeutic target in pancreatic ductal adenocarcinoma. Therefore, findings of research before the identification of estrogen receptor β should be reconsidered, and further studies should be designed to reassess the expression and effect of this specific estrogen receptor type in pancreatic cancer.

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Anthropometric and reproductive factors and the risk of pancreatic cancer: A case-control study in Shanghai, China

et al. 1996

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To examine the possible role of body size and reproductive factors in pancreatic cancer, data were analyzed from a population-based case-control study conducted in Shanghai, China.Cases (n = 45 I) were permanent residents of Shanghai, 30-74 years of age, newly diagnosed with pancreatic cancer between October I, 1990, and June 30, 1993. Deceased cases (I 9Oh) were excluded from the study. Controls (n = 1,552) were randomly selected from permanent Shanghai residents and frequencymatched to cases by gender and age. Information on body size and reproductive and other possible risk factors was collected through personal interviews. After adjustment for age, income, smoking and other confounders, a positive dose-response relation between body mass index and risk of pancreatic cancer was observed in both sexes. Among women, the risk of pancreatic cancer was significantly associated with number of pregnancies and live births. Compared with 0-2 pregnancies or live births, the odds ratio (OR) for 8 or more pregnancies was I .90. while that for 5 or more births was I .88. A modest elevation in risk, independent of parity, was associated with early age at first birth. Risk increased over 40% among women with a first birth at or before age 19 years relative to those at age 26 years or older. Ever use of oral contraceptives was associated with excess risk, though based on small numbers of users. Our findings suggest that, in Shanghai, obesity, gravidity, parity and perhaps use of oral contraceptives are associated with moderate increases in risk of pancreatic cancer, indicating that hormonal determinants deserve further investigation.o 1996 Wiley-Liss, Inc. * Epidemiologic studies have suggested a role for reproductive factors and steroidal hormones in the development of pancreatic cancer (Lin and Kessler, 1981;Bueno de Mesquita et al., 1992), but the evidence is limited. In addition, a positive association has been reported with body weight or obesity (Friedman and van den Eeden, 1993; M~l l e r et al., 1994). However, other studies have implicated height, but not weight, among women (Bueno de Mesquita et al., 1992), while still others have found no effect of weight (Kalapothaki et al., 1993).Since previous studies of pancreatic cancer have been carried out mainly in Western countries, we conducted a population-based case-control study of pancreatic cancer in Shanghai, China, where the incidence rates have been steadily rising over time (Jin et al., 1993). In earlier reports of this study, we have shown a positive relation with smoking and protective effects of fresh fruits and vegetables (Ji et al., 1995a, b). In this report, we examined the association with anthropometric and reproductive factors. MATERIAL AND METHODSData were derived from a population-based case-control study of gastro-intestinal cancers (pancreas, esophagus, colon and rectum) in urban Shanghai. The design has been described in detail elsewhere (Ji et al., 19956). Briefly, pancreatic cancer cases newly diagnosed between October 1, 1990, and June 30, 1993...

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Influence of sex hormones on pancreatic Cancer

Cited by 13 publications

References 34 publications

Sex Matters–Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer

Sex Matters–Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer

Estrogen Receptor Expression in Pancreatic Adenocarcinoma

Anthropometric and reproductive factors and the risk of pancreatic cancer: A case-control study in Shanghai, China

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