Response of metastatic mouse invasive lobular carcinoma to mTOR inhibition is partly mediated by the adaptive immune system.

Effective treatment of invasive lobular carcinoma (ILC) of the breast is hampered by late detection, invasive growth, distant metastasis, and poor response to chemotherapy. Phosphoinositide 3-kinase (PI3K) signaling, one of the major druggable oncogenic signaling networks, is frequently activated in ILC. We investigated treatment response and resistance to AZD8055, an inhibitor of mammalian target of rapamycin (mTOR), in the (KEP) mouse model of metastatic ILC.

Opiophobia in Cancer Biology- Justified? - The Role of Perioperative Use of Opioids in Cancer Recurrence.

Opioids remain the standard of care in the provision of analgesia in the patient undergoing cancer surgery preoperatively. The effects of opioids on tumor growth and metastasis have been discussed for many years. In recent years their use as part of the perioperative pain management bundle in the patients undergoing cancer surgery has been thought to promote cancer recurrence and metastasis.

Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of IL1β in tumor-associated macrophages.

Patients with primary solid malignancies frequently exhibit signs of systemic inflammation. Notably, elevated levels of neutrophils and their associated soluble mediators are regularly observed in cancer patients, and correlate with reduced survival and increased metastasis formation. Recently, we demonstrated a mechanistic link between mammary tumor-induced IL17-producing γδ T cells, systemic expansion of immunosuppressive neutrophils and metastasis formation in a genetically engineered mouse model for invasive breast cancer.

Regional anesthesia and analgesia in cancer care: is it time to break the bad news?

Purpose Of Review: There is ongoing controversy regarding the tumor-protective effects of regional anesthesia in patients undergoing cancer surgery. Evidence of up-to-date systematic reviews will be presented alongside recent updates on the effects of opioids and local anesthetics.

Recent Findings: In recent years, the literature regarding the effects of regional anesthesia techniques on cancer recurrence has raised many unanswered questions.

Perioperative Anesthesia Care and Tumor Progression.

This narrative review discusses the most recent up-to-date findings focused on the currently available "best clinical practice" regarding perioperative anesthesia care bundle factors and their effect on tumor progression. The main objective is to critically appraise the current literature on local anesthetics, regional outcome studies, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs) and their ability to decrease recurrence in patients undergoing cancer surgery. A brief discussion of additional topical perioperative factors relevant to the anesthesiologist including volatile and intravenous anesthetics, perioperative stress and anxiety, nutrition, and immune stimulation is included.

IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis.

Metastatic disease remains the primary cause of death for patients with breast cancer. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and their microenvironment. Within this local microenvironment and in distant organs, immune cells and their mediators are known to facilitate metastasis formation.

A preclinical mouse model of invasive lobular breast cancer metastasis.

Metastatic disease accounts for more than 90% of cancer-related deaths, but the development of effective antimetastatic agents has been hampered by the paucity of clinically relevant preclinical models of human metastatic disease. Here, we report the development of a mouse model of spontaneous breast cancer metastasis, which recapitulates key events in its formation and clinical course. Specifically, using the conditional K14cre;Cdh1(F/F);Trp53(F/F) model of de novo mammary tumor formation, we orthotopically transplanted invasive lobular carcinoma (mILC) fragments into mammary glands of wild-type syngeneic hosts.

Development of metastatic HER2(+) breast cancer is independent of the adaptive immune system.

The tumour-modulating effects of the endogenous adaptive immune system are rather paradoxical. Whereas some clinical and experimental observations offer compelling evidence for the existence of immunosurveillance, other studies have revealed promoting effects of the adaptive immune system on primary cancer development and metastatic disease. We examined the functional significance of the adaptive immune system as a regulator of spontaneous HER2(+) breast tumourigenesis and pulmonary metastasis formation, using the MMTV-NeuT mouse model in which mammary carcinogenesis is induced by transgenic expression of the activated HER2/neu oncogene.