INTRODUCTION: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome. METHOD: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice. RESULTS: Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4 + T cells, CD8 + T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group. CONCLUSION: CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases.
Background. Extrapulmonary inflammatory pseudotumor (plasma cell granuloma) is an uncommon lesion in adults and children, and little is known either of its etiology or clinical characteristics. However, it remains a significant source of morbidity to patients and confusion to clinicians.
Methods. Case reports are presented of three patients with intraabdominal inflammatory pseudotumor who recently underwent surgery. A review of the recent world literature is also presented. Clinical and laboratory characteristics of omental‐mesenteric inflammatory pseudotumor are reviewed along with a discussion of its etiology.
Results. Cytogenetic data from cells of one patient show a derivative chromosome evolved from a translocation between the long arm of chromosome 2 and the short arm of chromosome 9 [(2;9) (q1,3;p2,2)].
Conclusions. The lesion is monoclonal, and genetic changes may play a crucial role in the development of this neoplasm. Omental‐mesenteric inflammatory pseudotumor appears to represent a distinct clinicopathologic entity as a benign neoplasm in children. Cancer 1994; 73:1433–7.
Immunogenic cell death (ICD) activates both innate and adaptive arms of the immune system during apoptotic cancer cell death. With respect to cancer immunotherapy, the process of ICD elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity. Cancer ICD requires the presentation of various “hallmarks” of immunomodulation, which include the cell-surface translocation of calreticulin, production of type I interferons, and release of high-mobility group box-1 and ATP, which through their compatible actions induce an immune response against cancer cells. Interestingly, recent reports investigating the use of epigenetic modifying drugs as anticancer therapeutics have identified several connections to ICD hallmarks. Epigenetic modifiers have a direct effect on cell viability and appear to fundamentally change the immunogenic properties of cancer cells, by actively subverting tumor microenvironment-associated immunoevasion and aiding in the development of an antitumor immune response. In this review, we critically discuss the current evidence that identifies direct links between epigenetic modifications and ICD hallmarks, and put forward an otherwise poorly understood role for epigenetic drugs as ICD inducers. We further discuss potential therapeutic innovations that aim to induce ICD during epigenetic drug therapy, generating highly efficacious cancer immunotherapies.
Cervical teratomas are uncommon neoplasms. Although these lesions are histologically benign they are usually large and may cause airway obstruction. Cervical teratomas are usually diagnosed at birth. In-utero diagnosis is possible by prenatal ultrasound which assists in planning early airway management and surgical intervention. Mortality is significant but prognosis is good with airway control and complete surgical excision. However, pressure injury of contiguous structures can limit resectability and adversely affect outcome. Malignant cervical teratoma with metastasis has been reported mostly arising in adults with poor outcome. We present nine cases of neonatal cervical teratoma identified at two institutions between 1984 and 1996. One patient died before surgical intervention. All others underwent resection. There was one intraoperative death and one postoperative death. The remaining six patients did well postoperatively with no significant sequelae with 3 to 14 years follow-up.
NAD is a key metabolic redox cofactor that is regenerated from nicotinamide through the NAD salvage pathway. Here, we find that inhibiting the NAD salvage pathway depletes serine biosynthesis from glucose by impeding the NAD-dependent protein, 3-phosphoglycerate dehydrogenase (PHGDH). Importantly, we find that PHGDH breast cancer cell lines are exquisitely sensitive to inhibition of the NAD salvage pathway. Further, we find that PHGDH protein levels and those of the rate-limiting enzyme of NAD salvage, NAMPT, correlate in ER-negative, basal-like breast cancers. Although NAD salvage pathway inhibitors are actively being pursued in cancer treatment, their efficacy has been poor, and our findings suggest that they may be effective for PHGDH-dependent cancers.
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