Ewing sarcoma is a cancer that grows in the bones and soft tissues, usually in the thigh or pelvis. It is most common in children and young adults between the ages of 5 and 20, and more common in boys than girls. Although most patients are teenagers, Ewing sarcoma can sometimes occur in older adults … Read more
Twenty-year-old Amanda Lee has always wanted to be a nurse. But after a life-changing diagnosis in 2012, Lee suddenly had a more personal motivation to pursue her career goals. After seeing her primary care doctor for pain in her lower back, doctors determined Lee had a tumor that was causing internal bleeding. Lee, then 17, … Read more
Cancers known as sarcomas develop in the connective tissues, such as muscle, fat, and bone, that hold the body together. The type of sarcoma called liposarcoma originates in fat cells that have been driven by random DNA errors into malignant growth, forming tumors. George Demetri, MD, director of Dana-Farber’s Center for Sarcoma and Bone Oncology, … Read more
If your son or daughter has been diagnosed with a type of sarcoma – a tumor in connective tissue like muscles or bones – there are many questions: Will my child make a full recovery? What are the immediate and long-term side effects of treatment? Most parents don’t consider whether their child will face a … Read more
发布日期：2023年5月16日 医学审校：Robert J. Mayer博士（Robert J. Mayer, MD） 细胞周期包含一系列步骤，包括：活细胞生长、复制其DNA，并分裂成两个相同的子代细胞，每个子细胞获得母本的一份拷贝。当每个子细胞被封存在自身的膜内时，细胞周期完成，为开启新的细胞周期做好准备。 细胞周期以一种精确运转的方式展开，确保细胞将DNA的精准拷贝遗传给其子代细胞。在分裂前的DNA复制或DNA迁移到新形成的细胞的过程中，如果出现任何错误，那么细胞的遗传程序都会出错，从而导致癌症或其他疾病的产生。 细胞周期的分期（Stage） 在含有细胞核的细胞内，细胞周期有5个分期： G0期：细胞尚未分裂，在体内中正常运作 G1期（gap 1）：细胞生长 S期 (synthesis 合成) ：细胞复制其DNA G2期 (gap 2) ：细胞准备分裂 M期 (mitosis 有丝分裂) ：细胞核（nucleus）和细胞质（cytoplasm）分裂，形成两个子代细胞 人体细胞用90%的时间完成前三个分期， 统称分裂间期（interphase）。 细胞周期的持续时间因细胞类型而异。大部分人体细胞在24小时左右完成周期。快速生长的细胞（如肠道内壁细胞）或在9-10小时内完成分期，而肝细胞的分期则超过一年，神经细胞的分期则需更多年完成。 细胞分期和癌症 在细胞周期任何阶段出现的失误或错误——特别是在DNA复制或DNA分配给子细胞的过程中出错，都会驱使细胞向产生癌变的方向演化。 细胞周期含有若干检查点，其作用类似流水线上的阀门，让细胞“扫描”问题并采取必要的修复措施。细胞借此机会来确认自身生长到应有的大小、正确地复制了自身的DNA、准确地排列了用于分裂的染色体。细胞或修复错误，但如果严重的话，细胞也会通过自毁的方式避免将自身的错误传给后代。 若干蛋白质控制检查点，其中最重要的检查点之一是p53，它在细胞周期中主要在G1检查点上作用。当一个细胞的DNA受损时，一个蛋白质激活p53，p53终止细胞周期并下达修复的指令，如果出现不可修复的损伤，p53会引起细胞消亡。p53对健康细胞的延续而言至关重要，它也被视为基因组的护卫。 如果p53消失、发生故障或者比活性低于正常水平，它或许会让携带受损DNA的一个细胞进入细胞周期的下一阶段，增加DNA拼写错误且遗传给子细胞的几率。这种错误在多个细胞周期中不断累积，就会向癌症迈进一步。p53 是人类癌症中最常见的突变基因。 化疗如何影响细胞周期？ 在细胞周期的不同阶段，不同类型的化疗（chemotherapy）药物会对癌细胞发起攻击。 有些化疗药物对细胞周期的一个特定阶段作用。例如，抗代谢药（antimetabolite）和叶酸拮抗剂（antifol）就以S期为靶点，干扰DNA分子的构建。博来霉素（bleomycin）和依托泊苷（etoposide）和其它药物则以G2期为靶点，使DNA断裂；长春花生物碱类（vinca alkaloids）以M期为靶点，防止染色体在细胞分裂的过程中正确排列。 还有一些药物可作用于分裂中的细胞，无论细胞周期。这些药物包括：烷化剂（alkylating agents）——与DNA结合并阻止DNA复制；嵌入剂（intercalators）——起作用是扭曲DNA双螺旋的正常形状和结构。 第三类药物对癌细胞作用显著，无论癌细胞处在细胞周期的何种阶段。这些药物包括：皮质类固醇（corticosteroids）和激素拮抗剂（hormone antagonists），其作用机制是与细胞受体结合，防止细胞接收到生长信号。 放疗如何影响细胞周期？ 辐射会杀死处于积极分裂中的细胞，即不处于G0期的细胞。因为癌细胞无序生长，与正常细胞相比，它们或需要更多的时间完成分裂，所以癌细胞特别容易受到放疗的影响。 靶向治疗如何干预细胞周期？ 靶向疗法（targeted therapies）是一组抑制与癌症有关的特异性细胞蛋白质的药物。靶向疗法的药物有一部分作为标准治疗用药，有一些尚处于临床试验中，其核心聚焦于在细胞周期中起到关键作用的蛋白质。 以CDK4和CDK6蛋白质为例，这两种蛋白质在细胞周期的一个重要节点扮演着保护的作用，即细胞从G0期和G1期向S期过渡。在有些癌症病种中，CDK4和CDK6蛋白质的异常会使细胞分裂进入高速运转的状态。以CDK4/6抑制剂（CDK4/6 inhibitors）为代表的的药物干扰这些蛋白质，有助于阻止细胞周期的展开。在某些情况下，癌细胞不仅停止分裂，还会丧失所有用于循环和生长的能力，使得肿瘤缩小。CDK4/6抑制剂在治疗晚期雌激素受体阳性和HER2-阴性乳腺癌（advanced estrogen receptor-positive and HER2-negative breast … Read more
发布日期：2019年8月27日 更新时间：2023年6月2日 医学审校：Huma Q. Rana博士（Huma Q. Rana, MD, MPH） 关键摘要： CHEK2是一种肿瘤抑制基因，保护细胞免于癌变。 遗传基因突变的人群罹患某种癌症的风险有所加剧，更为频繁的筛查或可使其受益。 CHEK2是 “检测点激酶2（checkpoint kinase2）” 基因的缩写。该基因为血细胞生产CHK2蛋白质提供指令，当细胞里的DNA损毁或DNA链断裂时，CHK2被激活。 CHK2蛋白质有什么作用？ CHK2和其它基因响应DNA损坏的机制如下：通过终止细胞分裂并判断细胞之于人体健康应修复损伤还是自毁。这一过程确保了具有基因损伤或突变的细胞在分裂时，不会将 “有害” 的DNA传给下一代。这种基因突变可被视为迈向癌变的第一步。CHEK2使得细胞免于癌变，也被视为一种肿瘤抑制基因（tumor-suppressor gene）。 当CHEK2自身产生突变时（即构成CHEK2的DNA出错时），它的功能受损。在CHEK2基因不能正常作用时，细胞就失去了一个生长的关键限制，并且离无节制分裂的癌症更进一步。 哪些癌症携带CHEK2基因突变？ 美国国立卫生研究院（NIH）指出，很多癌症都有CHEK2基因突变，包括：乳腺癌、肾癌、甲状腺癌等。有些脑肿瘤和骨肉瘤（osteosarcoma，一种骨癌）也有CHEK2基因突变。 携带CHEK2突变的人群有哪些风险？ 携带CHEK2基因突变的人群罹患某些癌症的风险更高。携带CHEK2基因突变的女性罹患乳腺癌的风险是与未携带CHEK2基因突变的女性的两倍以上。因风险加剧，携带CHEK2基因突变的女性需要更为密切的乳房筛查。 结直肠癌、前列腺癌风险加剧是否与CHEK2基因突变相关尚不明确，但是携带CHEK2基因突变的人群需要与家庭医生和遗传学专家咨询，是否需要针对结直肠癌和前列腺癌展开筛查。 大部分携带CHEK2基因突变的个体都有该基因的一个正常基因的副本，以及一个突变的副本。因为子女从父母两人处分别集成一个基因的副本，因此携带CHEK2基因突变的人群遗传给子女的概率为50%。此外，因为CHEK2突变通常是通过基因传播的，所以知道自己携带CHEK2基因突变的人应该告诉近亲，以便他们根据自己的医院接受筛查检测。 近期有哪些CHEK2相关的科研信息？ CHEK2会发生许多不同的突变，包括该基因DNA的拼写错误。根据突变发生的位置，它们会从多方面影响基因：有些会关闭基因或阻止基因活性；或使得具有缺陷的CHEK2产生。 最近，由丹娜—法伯科学家Huma Rana博士和Brittany Bychkovsky博士带领的一项研究，对数千位患者的数据进行分析，以判断有些基因突变是否与某些特定类型的癌症相关。他们发现，无论患者携带哪种CHEK2基因突变，它都与乳腺癌、肾癌、甲状腺癌相关，与结直肠癌并不相关。此前，学界曾认为：在CHEK2基因突变患者中，结直肠癌更为常见。遗传学专家可根据以上研究，帮助先天携带CHEK2基因突变的患者更好地了解患癌的风险。 点击此处，从丹娜—法伯癌症研究所癌症遗传学和预防学诊所了解更多有关癌症风险的信息。 医学审校人简介： 2007年，Rana博士毕业于新泽西医学和牙科大学的罗伯特·伍德·约翰逊医学院（Robert Wood Johnson Medical School at the University of Medicine and Dentistry of New Jersey）。随后，她在西奈山医学院（Mount Sinai School of Medicine）完成了内科学住院医师培训，以及遗传学和基因科学专项培训。2020年，Rana博士在哈佛大学陈曾熙公共卫生学院获得公共卫生硕士学位。自2012年起，Rana博士在丹娜—法伯癌症研究所任职。 转载须知 … Read more
Patti Keenan was a senior in high school before learning that the mysterious disease she was treated for twice as a young girl in the 60s was, in fact, a rare form of cancer. Her parents, not wanting to frighten Patti at a time when pediatric cancer survival rates were much lower, kept their daughter’s … Read more
Like a mill crumbling into a river, solid tumors constantly shed bits of themselves — including their DNA — into the bloodstream. This free-floating genetic material, known as circulating tumor DNA, or ctDNA, contains a trove of information about the tumor. Advances in technology have made it possible to extract ctDNA from a blood sample, … Read more
The cell cycle is the series of steps by which living cells grow, duplicate their DNA, and divide into two identical daughter cells, each receiving one copy of the doubled material. The cycle is complete when each daughter cell is sealed in its own membrane, ready to start the cycle again. The cycle occurs in … Read more
Over the past three decades, the number of cancer survivors has increased. That trend is expected to continue. The numbers indicate progress in the treatment of cancer, but they also underscore the importance of quality of life after cancer. “We want people to lead healthy, productive, enjoyable lives, and mobility is such an important piece … Read more
在一项由丹娜—法伯癌症研究所带领的研究中，科学家们破解了某些DNA破损修复基因中的遗传性变异或加剧个体罹患尤因肉瘤（Ewing Sarcoma，也称尤文肉瘤）。尤因肉瘤常见于青少年和青壮年，是一种浸润性癌症。
A recent study found that women who frequently use chemical hair straighteners and relaxers could have a higher risk of developing uterine cancer than those who have not used the products. The study, which tracked 34,000 women nationwide for more than a decade, comes at a time when uterine cancer rates in women are increasing, … Read more
Uterine cancer — also known as endometrial cancer — has traditionally been classified as endometrioid or non-endometrioid based on the appearance of the tumor cells under a microscope. Now, as scientists learn more about the molecular makeup of the disease, uterine cancers are increasingly identified by the specific genetic alterations within them. Endometrioid uterine tumors … Read more
子宫癌（uterine cancer）也被称为子宫内膜癌（endometrial cancer）。一直以来，科学家们通过显微镜观察肿瘤细胞的外观，将子宫癌分为子宫内膜样（endometrioid）或非子宫内膜样（non-endometrioid）。如今，随着科学家们深入了解子宫癌的分子构成，子宫癌内部的特异性基因变化逐渐成为划分的考量因素。
Of all the mutated, blundering, havoc-wreaking genes in cancer cells, few are more ubiquitous than TP53. The gene, which in its normal, capable form is nicknamed the “guardian of the genome,” is found in a flawed form in almost every type of cancer, including up to half of all lung, ovarian, and colorectal cancers and … Read more
Among the most memorable on-air guests during the first WEEI/NESN Jimmy Fund Radio-Telethon — a live, 36-hour broadcast held each summer to benefit Dana-Farber patient care and research — was Todd Schwartz, a 19-year-old patient in Dana-Farber’s Jimmy Fund Clinic. Here, Todd’s mother, Janet Schwartz, reflects on her son’s appearance that day in 2002, his … Read more
Picture a floor strewn with broken crockery, hastily and haphazardly pieced back together, and you’ll have a sense of the chromosomal chaos inside many cancer cells. In a phenomenon known as chromothripsis, a chromosome or piece of chromosome shatters and reassembles almost randomly, mangling its genetic information. It’s a common feature of cancer cells, found … Read more
If COVID-19 has taught us anything, it’s that with funding and regulatory support, the scientific community can move quickly and produce miracles. So when President Joe Biden announced his commitment on Feb. 2, to cut cancer deaths by 50 percent over the next 25 years, it produced a wave of guarded optimism. “This is great … Read more
The immune cells known as natural killer (NK) cells are part of the body’s first line of defense against cancer. Many efforts are underway to harness NK cells as a form of cancer immunotherapy, but a critical question in the field remains: Why do some tumors tend to be sensitive to NK cells’ attacks while … Read more
Researchers at Dana-Farber and the Broad Institute of MIT and Harvard have created a novel Molecular Oncology Almanac that combines an algorithm, or computational method, for interpreting genomic alterations in a patient’s tumor, along with a knowledge base of molecular changes reported to be associated with tumor behavior. They say that the components of this … Read more