Microenvironment Determinants of Brain Metastasis

Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis

Arithmetic Branching Law and generic LL-packets

Let $G$ be a classical group defined over a local field $F$ of characteristic zero. For any irreducible admissible representation $\pi$ of $G(F)$, which is of Casselman-Wallach type if $F$ is archimedean, we extend the study of spectral decomposition of local descents in [JZ18] for special orthogonal groups over non-archimedean local fields to more general classical groups over any local field $F$. In particular, if $\pi$ has a generic local $L$-parameter, we introduce the spectral first occurrence index $\mathfrak{f}_{\mathfrak{s}}(\pi)$ and the arithmetic first occurrence index $\mathfrak{f}_{\mathfrak{a}}(\pi)$ of $\pi$ and prove in Theorem 1.4 that $\mathfrak{f}_{\mathfrak{s}}(\pi) = \mathfrak{f}_{\mathfrak{a}}(\pi)$. Based on the theory of consecutive descents of enhanced $L$-parameters developed in [JLZ22], we are able to show in Theorem 1.5 that the first descent spectrum consists of all discrete series representations, which determines explicitly the branching decomposition problem by means of the relevant arithmetic data and extends the main result ([JZ18, Theorem 1.7]) to the great generality.Comment: 31 pages, all comments welcomed. arXiv admin note: text overlap with arXiv:2207.0470

Chaihu Guizhi Ganjiang Decoction Ameliorates Pancreatic Fibrosis via JNK/mTOR Signaling Pathway

Pancreatic fibrosis is a pathological characteristic of chronic pancreatitis (CP) and pancreatic cancer. Chaihu Guizhi Ganjiang Decoction (CGGD) is a traditional Chinese medicine, which is widely used in the clinical treatment of digestive diseases. However, the potential anti-fibrosis mechanism of CGGD in treating CP remains unclear. Here, we conducted a series of experiments to examine the effect of CGGD on the CP rat model and primary isolated pancreatic stellate cells (PSCs). The results revealed that CGGD attenuated pancreatic damage, decreased collagen deposition, and inhibited PSC activation in the pancreas of CP rats. However, compared with the CP group, CGGD had no effect on body weight and serum amylase and lipase. In addition, CGGD suppressed autophagy by downregulating Atg5, Beclin-1, and LC3B and facilitated phosphorylation of mTOR and JNK in pancreatic tissues and PSCs. Moreover, the CGGD-containing serum also decreased LC3B or collagen I expression after rapamycin (mTOR inhibitor) or SP600125 (JNK inhibitor) treatment in PSCs. In conclusion, CGGD attenuated pancreatic fibrosis and PSC activation, possibly by suppressing autophagy of PSCs through the JNK/mTOR signaling pathway