Phosphorylated SHMT2 Regulates Oncogenesis Through m6A Modification in Lung Adenocarcinoma.

Targeting cancer-specific metabolic processes is a promising therapeutic strategy. Here, this work uses a compound library that directly inhibits metabolic enzymes to screen the potential metabolic targets in lung adenocarcinoma (LUAD). SHIN1, the specific inhibitor of serine hydroxymethyltransferase 1/2 (SHMT1/2), has a highly specific inhibitory effect on LUAD cells, and this effect depends mainly on the overexpression of SHMT2. This work clarifies that mitogen-activated protein kinase 1 (MAPK1)-mediated phosphorylation at Ser90 is the key mechanism underlying SHMT2 upregulation in LUAD and that this phosphorylation stabilizes SHMT2 by reducing STIP1 homology and U-box containing protein 1 (STUB1)-mediated ubiquitination and degradation. SHMT2-Ser90 dephosphorylation decreases S-adenosylmethionine levels in LUAD cells, resulting in reduced N6-methyladenosine (m6A) levels in global RNAs without affecting total protein or DNA methylation. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) analyses further demonstrate that SHMT2-Ser90 dephosphorylation accelerates the RNA degradation of oncogenic genes by reducing m6A modification, leading to the inhibition of tumorigenesis. Overall, this study elucidates a new regulatory mechanism of SHMT2 during oncogenesis and provides a theoretical basis for targeting SHMT2 as a therapeutic target in LUAD.

Application of magnetic resonance imaging radiomics in endometrial cancer: a systematic review and meta-analysis.

PURPOSE: We aimed to systematically assess the methodological quality and clinical potential application of published magnetic resonance imaging (MRI)-based radiomics studies about endometrial cancer (EC). METHODS: Studies of EC radiomics analyses published between 1 January 2000 and 19 March 2023 were extracted, and their methodological quality was evaluated using the radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pairwise correlation analyses and separate meta-analyses of studies exploring differential diagnoses and risk prediction were also performed. RESULTS: Forty-five studies involving 3 aims were included. The mean RQS was 13.77 (range: 9-22.5); publication bias was observed in the areas of 'index test' and 'flow and timing'. A high RQS was significantly associated with therapy selection-aimed studies, low QUADAS-2 risk, recent publication year, and high-performance metrics. Raw data from 6 differential diagnosis and 34 risk prediction models were subjected to meta-analysis, revealing diagnostic odds ratios of 23.81 (95% confidence interval [CI] 8.48-66.83) and 18.23 (95% CI 13.68-24.29), respectively. CONCLUSION: The methodological quality of radiomics studies involving patients with EC is unsatisfactory. However, MRI-based radiomics analyses showed promising utility in terms of differential diagnosis and risk prediction.

Chiral gem-difluoroalkyl reagents: gem-difluoroalkyl propargylic borons and gem-difluoroalkyl α-allenols.

Chiral fluorinated reagents provide new opportunities for the discovery of drugs and functional materials because the introduction of a fluorinated group significantly alters a molecule's physicochemical properties. Chiral gem-difluoroalkyl fragments (R-CF2-C*) are key motifs in many drugs. However, the scarcity of synthetic methods and types of chiral gem-difluoroalkyl reagents limits the applications of these compounds. Herein, we report two types of chiral gem-difluoroalkyl reagents chiral gem-difluoroalkyl propargylic borons and gem-difluoroalkyl α-allenols and their synthesis by means of methods involving rhodium-catalyzed enantioselective B-H bond insertion reactions of carbenes and Lewis acid-promoted allenylation reactions. The mild, operationally simple method features a broad substrate scope and good functional group tolerance. These two types of reagents contain easily transformable boron and alkynyl or allenyl moieties and thus might facilitate rapid modular construction of chiral molecules containing chiral gem-difluoroalkyl fragments and might provide new opportunities for the discovery of chiral gem-difluoroalkyl drugs and other functional molecules.

A systematic review and meta-analysis of CT and MRI radiomics in ovarian cancer: methodological issues and clinical utility.

OBJECTIVES: We aimed to present the state of the art of CT- and MRI-based radiomics in the context of ovarian cancer (OC), with a focus on the methodological quality of these studies and the clinical utility of these proposed radiomics models. METHODS: Original articles investigating radiomics in OC published in PubMed, Embase, Web of Science, and the Cochrane Library between January 1, 2002, and January 6, 2023, were extracted. The methodological quality was evaluated using the radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pairwise correlation analyses were performed to compare the methodological quality, baseline information, and performance metrics. Additional meta-analyses of studies exploring differential diagnoses and prognostic prediction in patients with OC were performed separately. RESULTS: Fifty-seven studies encompassing 11,693 patients were included. The mean RQS was 30.7% (range - 4 to 22); less than 25% of studies had a high risk of bias and applicability concerns in each domain of QUADAS-2. A high RQS was significantly associated with a low QUADAS-2 risk and recent publication year. Significantly higher performance metrics were observed in studies examining differential diagnosis; 16 such studies as well as 13 exploring prognostic prediction were included in a separate meta-analysis, which revealed diagnostic odds ratios of 25.76 (95% confidence interval (CI) 13.50-49.13) and 12.55 (95% CI 8.38-18.77), respectively. CONCLUSION: Current evidence suggests that the methodological quality of OC-related radiomics studies is unsatisfactory. Radiomics analysis based on CT and MRI showed promising results in terms of differential diagnosis and prognostic prediction. CRITICAL RELEVANCE STATEMENT: Radiomics analysis has potential clinical utility; however, shortcomings persist in existing studies in terms of reproducibility. We suggest that future radiomics studies should be more standardized to better bridge the gap between concepts and clinical applications.

Improved Carrier Lifetimes of CdSe Thin Film via Te Doping for Photovoltaic Application.

Cadmium selenide (CdSe) solar cells have proven to be a remarkable potential top cell for a silicon-based tandem application. However, the defects and short carrier lifetimes of CdSe thin films greatly limit the solar cell performance. In this work, a Te-doped strategy is proposed to passivate the Se vacancy defects and increase the carrier lifetime of the CdSe thin film. The theoretical calculation helps to reveal the mechanism of nonradiative recombination of the CdSe thin film in depth. After Te-doping, the calculated capture coefficient of CdSe can be reduced from 4.61 × 10-8 cm3 s-1 to 2.32 × 10-9 cm3 s-1. Meanwhile, the carrier lifetime of CdSe thin film is increased nearly 3-fold from 0.53 to 1.43 ns. Finally, the efficiency of the Cd(Se,Te) solar cell is improved to 4.11%, about a relative 36.5% improvement compared to the pure CdSe solar cell. Both theoretical calculations and experiments prove that Te can effectively passivate bulk defects and improve the carrier lifetime of CdSe thin films, deserving further exploration to improve solar cell performance.

Searching for Band-Dispersive and Defect-Tolerant Semiconductors from Element Substitution in Topological Materials.

Topological insulators and semimetal materials composed of heavy elements usually have inverted and dispersive band structures. It is interesting to notice that if lighter elements with reduced spin-orbit coupling are substituted for the heavy elements, the topological materials can be mutated into semiconductors with variable band gaps; for example, topological HgTe and Bi2Se3 can be mutated into CdTe and Sb2Se3, which are excellent optoelectronic semiconductors because the element substitution opens the band gap and meanwhile inherits the large band dispersion and high carrier mobility. Recently, many topological materials have been reported, and their databases have been built. Here, we demonstrate that these new topological materials can be used as the starting points to search for semiconductors with high carrier mobility and defect tolerance through element substitution. We take three recently discovered topological materials, Na3Bi, Pb2Bi2Te5, and EuCd2Sb2, as the benchmark systems to show the general validity of this strategy and find that the derived Na3P, Na3As, Sn2Sb2S5, and CaZn2N2 are all band-dispersive and defect-tolerant semiconductors with potential optoelectronic applications. For Na3P, Na3As, and Na3Sb, the new P3̅c1 structure derived from the topological Na3Bi is found unexpectedly to be their ground-state structure, more stable than their well-known structures reported in the literature. This study not only gains new insights into the physical properties of these semiconductors but also proposes an effective strategy for the search of band-dispersive and defect-tolerant semiconductors that can be generalized to other topological materials.

Emerging Chalcogenide Thin Films for Solar Energy Harvesting Devices.

Chalcogenide semiconductors offer excellent optoelectronic properties for their use in solar cells, exemplified by the commercialization of Cu(In,Ga)Se2- and CdTe-based photovoltaic technologies. Recently, several other chalcogenides have emerged as promising photoabsorbers for energy harvesting through the conversion of solar energy to electricity and fuels. The goal of this review is to summarize the development of emerging binary (Sb2X3, GeX, SnX), ternary (Cu2SnX3, Cu2GeX3, CuSbX2, AgBiX2), and quaternary (Cu2ZnSnX4, Ag2ZnSnX4, Cu2CdSnX4, Cu2ZnGeX4, Cu2BaSnX4) chalcogenides (X denotes S/Se), focusing especially on the comparative analysis of their optoelectronic performance metrics, electronic band structure, and point defect characteristics. The performance limiting factors of these photoabsorbers are discussed, together with suggestions for further improvement. Several relatively unexplored classes of chalcogenide compounds (such as chalcogenide perovskites, bichalcogenides, etc.) are highlighted, based on promising early reports on their optoelectronic properties. Finally, pathways for practical applications of emerging chalcogenides in solar energy harvesting are discussed against the backdrop of a market dominated by Si-based solar cells.

Effective lifetime of non-equilibrium carriers in semiconductors from non-adiabatic molecular dynamics simulations.

The lifetimes of non-equilibrium charge carriers in semiconductors calculated using non-adiabatic molecular dynamics often differ from experimental results by orders of magnitude. By revisiting the definition of carrier lifetime, we report a systematic procedure for calculating the effective carrier lifetime in semiconductor crystals under realistic conditions. The consideration of all recombination mechanisms and the use of appropriate carrier and defect densities are crucial to bridging the gap between modeling and measurements. Our calculated effective carrier lifetime of CH3NH3PbI3 agrees with experiments, and is limited by band-to-band radiative recombination and Shockley-Read-Hall defect-assisted non-radiative recombination, whereas the band-to-band non-radiative recombination is found to be negligible. The procedure is further validated by application to the compound semiconductors CdTe and GaAs, and thus can be applied in carrier lifetime simulations in other material systems.

Controllable Doping in 2D Layered Materials.

For each generation of semiconductors, the issue of doping techniques is always placed at the top of the priority list since it determines whether a material can be used in the electronic and optoelectronic industry or not. When it comes to 2D materials, significant challenges have been found in controllably doping 2D semiconductors into p- or n-type, let alone developing a continuous control of this process. Here, a unique self-modulated doping characteristic in 2D layered materials such as PtSSe, PtS0.8 Se1.2 , PdSe2 , and WSe2 is reported. The varying number of vertically stacked-monolayers is the critical factor for controllably tuning the same material from p-type to intrinsic, and to n-type doping. Importantly, it is found that the thickness-induced lattice deformation makes defects in PtSSe transit from Pt vacancies to anion vacancies based on dynamic and thermodynamic analyses, which leads to p- and n-type conductance, respectively. By thickness-modulated doping, WSe2 diode exhibits a high rectification ratio of 4400 and a large open-circuit voltage of 0.38 V. Meanwhile, the PtSSe detector overcomes the shortcoming of large dark-current in narrow-bandgap optoelectronic devices. All these findings provide a brand-new perspective for fundamental scientific studies and applications.

More Se Vacancies in Sb2 Se3 under Se-Rich Conditions: An Abnormal Behavior Induced by Defect-Correlation in Compensated Compound Semiconductors.

It was believed that the Se-rich synthesis condition can suppress the formation of deep-level donor defect VSe (selenium vacancy) in Sb2 Se3 and is thus critical for fabricating high-efficiency Sb2 Se3 solar cells. However, here it is shown that by first-principles calculations the density of VSe increases unexpectedly to 1016 cm-3 when the Se chemical potential increases, so Se-rich condition promotes rather than suppresses the formation of VSe . Therefore, high density of VSe is thermodynamically inevitable, no matter under Se-poor or Se-rich conditions. This abnormal behavior can be explained by a physical concept "defect-correlation", i.e., when donor and acceptor defects compensate each other, all defects become correlated with each other due to the formation energy dependence on Fermi level which is determined by densities of all ionized defects. In quasi-1D Sb2 Se3 , there are many defects and the complicated defect-correlation can give rise to abnormal behaviors, e.g., lowering Fermi level and thus decreasing the formation energy of ionized donor VSe 2+ in Se-rich Sb2 Se3 . Such behavior exists also in Sb2 S3 . It explains the recent experiments that the extremely Se-rich condition causes the efficiency drop of Sb2 Se3 solar cells, and demonstrates that the common chemical intuition and defect engineering strategies may be invalid in compensated semiconductors.

Extracellular Vesicles in Tumor Diagnosis: A Mini-Review.

Wide exploration of noninvasive tumor/cancer biomarkers has shed light on clinical diagnosis. However, many under-investigated biomarkers showed limited application potency due to low sensitivity and specificity, while extracellular vehicles (EVs) were gradually recognized as promising candidates. EVs are small vesicles transporting bioactive cargos between cells in multiple physiological processes and also in tumor/cancer pathogenesis. This review aimed to offer recent studies of EVs on structure, classification, physiological functions, as well as changes in tumor initiation and progression. Furthermore, we focused on advances of EVs and/or EV-related substances in cancer diagnosis, and summarized ongoing studies of promising candidates for future investigations.

A pH-responsive Pickering Nanoemulsion for specified spatial delivery of Immune Checkpoint Inhibitor and Chemotherapy agent to Tumors.

Rationale: Immune checkpoint (ICP) blockade therapy combined with chemotherapy is a promising treatment strategy for tumors. Chemotherapeutic agents usually function inside the tumor cells, while ICP inhibitors are efficacious out of the tumor cells. It is desirable to effectively co-deliver an ICP inhibitor and a chemotherapy agent to different sites of a tumor. We have designed an effective drug delivery system to accomplish both objectives. Methods: We designed a Pickering nanoemulsion (PNE) using multi-sensitive nanogels with pH-responsive, hydrophilicity-hydrophobicity switch, and redox-responding properties as an oil/water interfacial stabilizer. The D/HY@PNE was employed for specified spatial delivery of the chemotherapy agent doxorubicin (DOX) and ICP inhibitor HY19991 (HY). We systematically investigated the pH-responsive disassembly of PNE, the release of DOX and HY from D/HY@PNE in the tumor microenvironment, enhanced tumor penetration of DOX, immunogenic cell death (ICD), antitumor efficacy, and the immune response induced by D/HY@PNE in vitro and in vivo. Results: D/HY@PNE disassembled to release the ICP inhibitor HY and DOX-loaded nanogels due to the hydrophilicity-hydrophobicity reversal of nanogels in the acidic tumor microenvironment. Quantitative analysis indicates that D/HY@PNE presents enhanced tumor penetration behavior and effectively induces ICD. The strong immune response induced by D/HY@PNE was due to the efficient synergetic combination of chemotherapy and immunotherapy and resulted in enhanced antitumor efficacy in 4T1 tumor-bearing mice. Conclusion: This novel strategy highlights the promising potential of a universal platform to co-deliver different therapeutic or diagnostic reagents with spatial regulation to improve the anti-tumor effect.

Quasi-one-dimensional Sb2(S,Se)3 alloys as bandgap-tunable and defect-tolerant photocatalytic semiconductors.

Both Sb2S3 and Sb2Se3 have been studied as promising photocatalytic and photovoltaic semiconductors because of their suitable bandgaps, high light absorption coefficients and good stability. Through forming the mixed-anion Sb2(S,Se)3 alloys, the bandgaps and lattice parameters can be tuned and a band structure engineering design of semiconductor heterostructures becomes possible. However, the properties of the disordered Sb2(S,Se)3 alloys are currently not clear. Using first-principles calculations, we show that the alloys are highly miscible with low formation enthalpies, so composition-variable and uniform alloys can be fabricated under room temperature. The bandgaps of the alloys change almost linearly as the alloy composition (S/Se ratio) varies, indicating that the bandgap engineering can be quite flexible. The calculations of the defect properties show that there are dozens of detrimental defects producing deep levels in the bandgap of the alloy under the Sb-rich (Se-poor) condition, which can cause serious electron-hole non-radiative recombination and limit the minority carrier lifetime. The formation of these detrimental defects can be largely suppressed under the Sb-poor condition, so we propose that the Sb-poor (Se-rich) condition should be adopted for fabricating Sb2(S,Se)3 alloys as photocatalytic and photovoltaic light-absorber semiconductors with long minority carrier lifetimes.

Complicated and Unconventional Defect Properties of the Quasi-One-Dimensional Photovoltaic Semiconductor Sb2Se3.

It was expected that the properties of intrinsic point defects would be simple in the binary semiconductor Sb2Se3. However, we show using first-principles calculations that the intrinsic defects in this quasi-one-dimensional (Q1D) semiconductor are unexpectedly complicated and different from those in conventional photovoltaic semiconductors such as CdTe or GaAs. First, the same type of defects located on non-equivalent atomic sites can have very different properties due to the low symmetry of the Q1D structure, which makes the properties of point defects complicated, even though there are only a few point defects. Second, uncommon defects such as the cation-replace-anion antisite SbSe, anion-replace-cation antisite SeSb, and even two-anion-replace-one-cation antisite 2SeSb, which are difficult to form in CdTe and GaAs, can have high concentrations and even be dominant in Sb2Se3 due to the weak van der Waals interactions and the large void space between different [Sb4Se6] n atomic chains of the Q1D structure. These defects produce a series of acceptor and donor levels in the band gap and make Sb2Se3 p-type under the Se-rich condition but n-type under the Se-poor condition. Five deep-level recombination-center defects are identified, and their formation is difficult to suppress, imposing a serious limit to the development of high-efficiency Sb2Se3 solar cells. Our study demonstrates that the defects can be complicated and unconventional in the binary compound semiconductors with low symmetry and Q1D structures, which can be classified as chemically binary while structurally multinary.

Organic-Inorganic Layered and Hollow Tin Bromide Perovskite with Tunable Broadband Emission.

Recently, layered perovskites attracted great attention for its excellent stability and light-emitting property. However, most of them rely on the toxic element lead and their emission quantum yields are generally low. Here, a unique hollow two-dimensional perovskite was developed in which the organic hexamethylene diamines (C6H18N22+) strongly coupled with distorted tin bromide anions (SnBr64-). This toxic-free low-dimensional tin perovskite exhibits a broadband emission in the visible region with a high luminescence quantum yield of 86%. First-principles calculation indicate the broadband emission is associated with the recombination of self-trapped excitons. And the emission is related to the geometry of tin bromide anions. An ultraviolet light-pumped white light emitting diode with excellent color-rendering index of 94 was fabricated using it together with a commercially available blue phosphor.

Successful management of perivascular epithelioid cell tumor of the rectum with recurrent liver metastases: A case report.

RATIONALE: The perivascular epithelioid cell tumor (PEComa) is rare in young man and rarely occurs in the large intestine. PATIENT CONCERNS: The clinical characteristics, diagnosis, and managements in a 28-year-old boy who presented with sudden onset of cramping and abdominal pain and intermittent melena with a blood pressure of 74/39 mm Hg was retrospectively reviewed. CT scan of the abdomen revealed a 8.9 × 7.2 cm mass in the pelvic floor. DIAGNOSES: Given the difficulty of obtaining a diagnostic specimen, surgical resection was performed. The pathology report of lower anterior resection was malignant PEComa of the rectum in 2006. INTERVENTIONS: Treatment consisted of surgical resection only without additional adjuvant therapy. Over the next 49 months (until 2010) after surgery, abdominal CT showed a 0.6-cm hypodense mass over the liver with suspected liver metastasis. He refused any further evaluation and treatment. After 4 years (2014), abdominal CT showed that the original mass had increased from 0.6 to 1.5 cm and the number of tumors had increased from 1 to 3. In August 2014, he underwent a metastatic hepatectomy without additional chemotherapy or radiotherapy. OUTCOMES: We noted that the metastatic progression was slow in the 4 years after the first operation. At 28 months after metastatic hepatectomy, the patient was doing well. There was also no recurrence of the PEComa of the rectum at the 120-month follow-up in 2016. LESSONS: To the best of our knowledge, this is the first report of a PEComa of the rectum with liver metastases treated with only surgical resection. At approximately 8.8 cm, this is the largest PEComa of the rectum reported in the recent literature.

Clinical Implication of UGT1A1 Promoter Polymorphism for Irinotecan Dose Escalation in Metastatic Colorectal Cancer Patients Treated with Bevacizumab Combined with FOLFIRI in the First-line Setting.

PURPOSE: This study aimed to identify the efficacy and toxicity of the FOLFIRI regimen (fluorouracil, leucovorin, and irinotecan) with irinotecan dose escalation plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer (mCRC) via UGT1A1 genotyping. METHODS: We administered bevacizumab plus FOLFIRI with irinotecan dose escalation to treat 70 mCRC patients. The UGT1A1 *1/*1 and *1/*28 genotypes started with a 180-mg/m(2) dose of irinotecan, and UGT1A1 *28/*28 genotype started with a dose of 120 mg/m(2). The dose of irinotecan was escalated at increasing intervals of 20 to 30 mg/m(2) until grade 3/4 adverse events (AEs) occurred. The clinical response rate, toxicity, and survival were analyzed. RESULTS: The clinical response and disease control rates of mCRC patients treated with FOLFIRI plus bevacizumab were significantly better in patients with UGT1A1 *1/*1 and *1/*28 genotypes than in patients with UGT1A1 *28/*28 (P = .006 and P < .001, respectively). Grade 3/4 AEs were significantly more common in mCRC patients with the UGT1A1 *28/*28 genotype (P < .001). Progression-free survival was significantly higher in UGT1A1 *1/*1 and *1/*28 patients (P = .002). mCRC patients who underwent metastasectomy achieved better overall survival than those who did not undergo metastasectomy (P = .015). CONCLUSIONS: Our study showed that mCRC patients with UGT1A1 *1/*1 and *1/*28 genotypes could receive escalated doses of irinotecan to obtain a more favorable clinical outcome without significant AEs.

FOLFIRI combined with bevacizumab as first-line treatment for metastatic colorectal cancer patients with hyperbilirubinemia after UGT1A1 genotyping.

OBJECTIVE: To report a metastatic colorectal cancer patient with hyperbilirubinemia treated with a combination of bevacizumab and FOLFIRI (5-fluorouracil, leucovorin, and irinotecan) using uridine diphosphate glucuronosyl transferase (UGT1A1) genotyping. CLINICAL PRESENTATION AND INTERVENTION: A 46-year-old male was diagnosed with rectosigmoid colon cancer with liver metastases and hyperbilirubinemia presenting with severe jaundice. UGT1A1 genotyping was used before therapy to ascertain whether genotype-adjusted dosages of irinotecan plus bevacizumab could alleviate the toxicity. Then, the patient was treated with FOLFIRI. CONCLUSION: The FOLFIRI regimen was successfully used in this patient without concerns regarding toxicity.

Prognostic advantage of irinotecan dose escalation according to uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping in patients with metastatic colorectal cancer treated with bevacizumab combined with 5-fluorouracil/leucovorin with irinotecan in a first-line setting.

This study compared the clinical responses of patients with metastatic colorectal cancer (mCRC) with 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) plus bevacizumab therapy either with or without uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping and irinotecan dose escalation. Of 107 total patients with mCRC, 79 were classified as the study group and 28 as the control group. The study group received irinotecan dose escalation based on UGT1A1 genotyping whereas the control group did not. Clinicopathologic features, response rates, and survival were compared for the 2 groups. The clinical response rate of patients with mCRC treated with FOLFIRI plus bevacizumab under UGT1A1 genotyping and irinotecan dose escalation was significantly better than that of those without these prospective tests and dose escalation (P = 0.028). Both progression-free survival (PFS) and overall survival were significantly greater in clinical responders than nonresponders (both, P < 0.001), and PFS was significantly greater among the study group patients than among the control group patients, with a median PFS of 12.2 months vs 9.4 months (P = 0.025). Grade 3/4 adverse events were not significantly different between the 2 groups (P = 0.189). Patients with mCRC undergoing UGT1A1 genotyping may receive escalated doses of irinotecan to obtain a better clinical response/outcome with comparable toxicities.

Polymorphisms in XPD and ERCC1 Associated with Colorectal Cancer Outcome.

Using the comprehensive approach to selecting polymorphisms to date, we sought to examine whether recurrence in colorectal cancer was associated with inherited variation in three genes involved in DNA repair and cell proliferation. Three polymorphisms, which are excision repair cross-complementation 1 (ERCC1), xeroderma pigmentosum group D (XPD) and epidermal growth factor receptor (EGFR), were assessed in 257 postoperative stage II/III CRC patients with 5-fluorouracial chemotherapy in Taiwan. In addition, the correlations between genetic polymorphisms and patients' clinicopathological features were investigated. Genotypes of XPD codon751 A/A and ERCC1 codon118 T/T were associated with regional recurrence in a statistically significant way (p = 0.018). Patients who carried XPD AA and ERCC1 TT genotypes demonstrated a significantly greater regional recurrence risk (OR = 5.625, 95% CI, 1.557-20.32). Inherited variation in XPD and ERCC1 was associated with outcome in patients with colorectal cancer in Taiwan. As the significant association of single-nucleotide polymorphisms has not been studied previously in colorectal cancer, these findings suggest novel sites of variation, in part explaining the range of treatment responses seen in this disease.