IN VIVO ~1 H MAGNETIC RESONANCE SPECTROSCOPY IN EVALUATION OF HEPATOCELLULAR CARCINOMA AND ITS EARLY RESPONSE TO TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION

Objective To investigate the value of in vivo proton magnetic resonance spectroscopy （MRS） in the assessment of hepatocelhilar carcinoma （HCC） and monitor its metabolic change shortly after transcatheter arterial chemoembolization （TACE）. Mothoda In this prospective study, 28 consecutive patients with large HCC （ ≥3 cm in diameter） confirmed by fine needle aspiration biopsy were recruited. The ^1H MRS of all hepatic lesions and some uninvolved liver parenchyma were performed with 1.5T whole body MR scanner. Among them, 15 cases were evaluated again about one week after TACE. The main metabolites such as choline and lipid before and after interventional therapy were measured to assess the early response of the tumor. The technical success rate of IH MRS in liver was high （33/41, 80% ）, closely related to breath motion, location of lesion, and size of voxeL In spectra, the choline compound peak of HCC elevated compared with uninvolved liver parenchyma. After TACE, both the amplitude and the area of choline resonance peak significantly descended （ choline-to-lipid ratios from 0.352±0. 080 to 0. 167±0. 030, P = 0. 026; from 0. 205±0. 060 to 0. 070±0. 020, P = 0. 042, respectively ） ; yet lipid resonance peak ascended. Conclusions In vivo tH MRS is technically feasible for the evaluation of large focal hepatic lesions, however, the reproducibility and stability are not as good as routine MR scan. IH MRS can monitor the early stage metabolic changes of HCC after TACE but limitation like quantification still exists.

Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis

AIM: To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H NMR) combined with principal components analysis (PCA) and evaluate the radiotherapeutic effect. METHODS: The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm3 , the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. 1H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiationtreated pancreatic tumor tissues were compared. RESULTS: Compared with 1H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the 1H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased. CONCLUSION: The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.

Bidirectional crosstalk between therapeutic cancer vaccines and the tumor microenvironment:Beyond tumor antigens

Immunotherapy has rejuvenated cancer therapy,especially after anti-PD-(L)1 came onto the scene.Among the many therapeutic options,therapeutic cancer vaccines are one of the most essential players.Although great progress has been made in research on tumor antigen vaccines,few phase III trials have shown clinical benefits.One of the reasons lies in obstruction from the tumor microenvironment(TME).Meanwhile,the therapeutic cancer vaccine reshapes the TME in an ambivalent way,leading to immune stimulation or immune escape.In this review,we summarize recent progress on the interaction between therapeutic cancer vaccines and the TME.With respect to vaccine resistance,innate immunosuppressive TME components and acquired resistance caused by vaccination are both involved.Understanding the underlying mechanism of this crosstalk provides insight into the treatment of cancer by directly targeting the TME or synergizing with other therapeutics.