Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness

In this study, we show that distinct compartmentalization patterns of the IL-1 molecules (IL-1alpha and IL-1beta), in the milieu of tumor cells that produce them, differentially affect the malignant process. Active forms of IL-1, namely precursor IL-1alpha (pIL-1alpha), mature IL-1beta (mIL-1beta), and mIL-1beta fused to a signal sequence (ssIL-1beta), were transfected into an established fibrosarcoma cell line, and tumorigenicity and antitumor immunity were assessed. Cell lines transfected with pIL-1alpha, which expresses IL-1alpha on the membrane, fail to develop local tumors and activate antitumor effector mechanisms, such as CTLs, NK cells, and high levels of IFN-gamma production. Cells transfected with secretable IL-1beta (mIL-1beta and ssIL-1beta) were more aggressive than wild-type and mock-transfected tumor cells; ssIL-1beta transfectants even exhibited metastatic tumors in the lungs of mice after i.v. inoculation (experimental metastasis). In IL-1beta tumors, increased vascularity patterns were observed. No detectable antitumor effector mechanisms were observed in spleens of mice injected with IL-1beta transfectants, mock-transfected or wild-type fibrosarcoma cells. Moreover, in spleens of mice injected with IL-1beta transfectants, suppression of polyclonal mitogenic responses (proliferation, IFN-gamma and IL-2 production) to Con A was observed, suggesting the development of general anergy. Histologically, infiltrating mononuclear cells penetrating the tumor were seen at pIL-1alpha tumor sites, whereas in mIL-1beta and ssIL-1beta tumor sites such infiltrating cells do not penetrate inside the tumor. This is, to our knowledge, the first report on differential, nonredundant, in vivo effects of IL-1alpha and IL-1beta in malignant processes; IL-1alpha reduces tumorigenicity by inducing antitumor immunity, whereas IL-1beta promotes invasiveness, including tumor angiogenesis, and also induces immune suppression in the host

Simultaneous occurrence of medullary and papillary thyroid microcarcinomas: a case series and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Papillary thyroid microcarcinoma has been demonstrated to present in association with medullary thyroid carcinoma, however, medullary thyroid carcinoma and papillary thyroid carcinoma represent rare entities. In recent years this rarity has been increasingly observed. The pathogenesis is still controversial. Genetic analysis of <it>RET</it> proto-oncogenes in cases of simultaneous papillary thyroid carcinoma and medullary thyroid carcinoma has so far provided conflicting results; although it seems that germline mutations play a potential role in the development of both histological types.</p> <p>Case presentations</p> <p>This paper describes four rare cases of simultaneous medullary thyroid carcinoma and papillary thyroid microcarcinoma with unique features:</p> <p>Case one was a 43-year-old Jewish woman, born in Israel, daughter of a Latvian immigrant mother and a father born in Israel. Case two was a 44-year-old Arab woman born in Israel. Case three was a 45-year-old Jewish woman, born in Israel, daughter of Moroccan immigrant parents and is unique for the presence of lymph node metastatic medullary thyroid carcinoma, and one lymph node with metastatic papillary carcinoma found in the same side. Case four was a 77-year-old Jewish woman, born in Iraq. These cases are unique in their composition of thyroid carcinoma, consisting of histologic features of medullary thyroid carcinoma, papillary thyroid microcarcinoma, and follicular thyroid adenoma. The four cases represent different ethnicity groups that live in north Israel, and case four is notable for the advanced age of the patient (77 years).</p> <p>Conclusion</p> <p>These four cases add more data supporting the coincidental coexistence of papillary thyroid microcarcinoma and medullary thyroid carcinoma; our results may suggest that the simultaneous occurrence of medullary thyroid carcinoma and papillary thyroid microcarcinoma is generally a simple reflection of this coincidence. Endocrinologists and pathologists should be aware of this entity. The pathologist can play a pivotal role in identifying papillary thyroid microcarcinoma in concurrent existence with medullary thyroid carcinoma.</p